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22q11.2 deletion syndrome laboratory findings

2020-08-28T00:29:54Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

Please help WikiDoc by adding more content here. It's easy! Click [[Help:How_to_Edit_a_Page|here]] to learn about editing.

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
Patients diagnosed with or suspected of having DGS should undergo extensive evaluation, particularly if life-threatening cardiac or immunologic deficits are present.

Testing for CBC, T and B lymphocyte panels, Echocardiography, Immunoglobulin levels, Calcium levels are some of the main ones for evaluating DGS.

==Laboratory Findings==
Patients diagnosed with or suspected of having DGS should undergo extensive evaluation, particularly if life-threatening cardiac or immunologic deficits are present. The following tests should merit consideration:

Echocardiogram to evaluate conotruncal abnormalities

Complete blood count with differential

T and B Lymphocyte subset panels

Flow cytometry to assess T cell repertoire

Immunoglobulin levels

Vaccine titers for evaluation of response to vaccines

Serum ionized calcium and phosphorus levels

Parathyroid hormone level

Chest x-ray for thymic shadow evaluation

Renal ultrasound for possible renal and genitourinary defects

Serum creatinine

TSH

Testing for growth hormone deficiency

It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features. Implementation of advancing genomic studies and facial recognition technology in modern medicine may assist in more effective diagnosis and evaluation of DGS patients.<ref>Kruszka P, Addissie YA, McGinn DE, Porras AR, Biggs E, Share M, Crowley TB, Chung BH, Mok GT, Mak CC, Muthukumarasamy P, Thong MK, Sirisena ND, Dissanayake VH, Paththinige CS, Prabodha LB, Mishra R, Shotelersuk V, Ekure EN, Sokunbi OJ, Kalu N, Ferreira CR, Duncan JM, Patil SJ, Jones KL, Kaplan JD, Abdul-Rahman OA, Uwineza A, Mutesa L, Moresco A, Obregon MG, Richieri-Costa A, Gil-da-Silva-Lopes VL, Adeyemo AA, Summar M, Zackai EH, McDonald-McGinn DM, Linguraru MG, Muenke M. 22q11.2 deletion syndrome in diverse populations. Am. J. Med. Genet. A. 2017 Apr;173(4):879-888.</ref>
==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

22q11.2 deletion syndrome laboratory findings

2020-08-28T00:29:22Z

Ayushijain: /* Laboratory Findings */

__NOTOC__
{{22q11.2 deletion syndrome}}

Please help WikiDoc by adding more content here. It's easy! Click [[Help:How_to_Edit_a_Page|here]] to learn about editing.

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
Patients diagnosed with or suspected of having DGS should undergo extensive evaluation, particularly if life-threatening cardiac or immunologic deficits are present.

Testing for CBC, T and B lymphocyte panels, Echocardiography, Immunoglobulin levels, Calcium levels are some of the main ones for evaluating DGS.

==Laboratory Findings==
Patients diagnosed with or suspected of having DGS should undergo extensive evaluation, particularly if life-threatening cardiac or immunologic deficits are present. The following tests should merit consideration:

Echocardiogram to evaluate conotruncal abnormalities

Complete blood count with differential

T and B Lymphocyte subset panels

Flow cytometry to assess T cell repertoire

Immunoglobulin levels

Vaccine titers for evaluation of response to vaccines

Serum ionized calcium and phosphorus levels

Parathyroid hormone level

Chest x-ray for thymic shadow evaluation

Renal ultrasound for possible renal and genitourinary defects

Serum creatinine

TSH

Testing for growth hormone deficiency

It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features. Implementation of advancing genomic studies and facial recognition technology in modern medicine may assist in more effective diagnosis and evaluation of DGS patients.

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

22q11.2 deletion syndrome epidemiology and demographics

2020-08-28T00:21:56Z

Ayushijain: /* Epidemiology and Demographics */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
The estimated prevalence has been cited in several studies as being 1:3000-1:6000 births.<br />Currently, the figures are 6%-10% of new cases are familial. Since survival with cardiac anomalies was low until the mid-1980s, the familial cases are expected to rise.

==Epidemiology and Demographics==
The estimated prevalence has been cited in several studies as being 1:3000-1:6000 births. These estimates are based on extrapolations of limited populations that have been screened using fluorescent in situ hybridization (FISH) technology. Males and females are equally affected, and there is no population "founder" effect. The deletion arises de novo frequently in all populations, and there is no reason to believe that the syndrome is more frequent in any particular ethnic background. The existing data do not yet take into account the rising prevalence due to increasing numbers of affected adults having their own affected children. Since this is a haplosufficiency disorder, one-half of the children of affected adults will have the deletion. Therefore, the prevalence is anticipated to rise over time. Currently, the figures are 6%-10% of new cases are familial. Since survival with cardiac anomalies was low until the mid-1980s, the familial cases are expected to rise.

Recent studies using SNP arrays have suggested that there are atypical deletions not detected by FISH-based strategies, and the true prevalence may be higher than suspected when these variants are included.

Commercial laboratories have reported classical deletions in approximately 1:100-1:200 samples sent for SNP array testing, and atypical deletions with approximately half of that frequency (Lisa Shaffer, Signature Genomics, personal communication). These laboratory sets represent patient cohorts with underlying medical problems but give valuable information on the relative frequencies of the typical and atypical deletions. Many of the atypical deletions would not have been identified with FISH technology, leading to the belief that we currently underascertain patients with the deletion.

While the frequency in the general population is slightly less frequent than trisomy 21, it is still sufficiently common that chromosome 22q11.2 deletion can occur in combination with other diagnoses. We have seen patients with Marfan syndrome and chromosome 22q11.2 deletion syndrome, Ehlers-Danlos and chromosome 22q11.2 deletion syndrome, and trisomy 21 and chromosome 22q11.2 deletion syndrome. There have also been distant family members with the deletion where it arose on completely distinct haplotypes and therefore represent distinct de novo events.

An important clinical aspect in the consideration of the demographic characteristics of the deletion is the frequency in unselected populations with compatible phenotypic features. The variability of the phenotypic features has made it difficult to define the exact clinical scenario where testing is warranted. Various algorithms have been developed to identify patient groups for whom testing for the deletion is clearly clinically warranted. These algorithms have thus far been disappointing at identifying patients outside of the most classic phenotype. Nevertheless, multiple studies have identified the frequency of the deletion in specific patient groups, and these data provide valuable context when considering the diagnostic approach.

==References==
{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome epidemiology and demographics

2020-08-28T00:20:27Z

Ayushijain: /* Epidemiology and Demographics */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
<br />

==Epidemiology and Demographics==
The estimated prevalence has been cited in several studies as being 1:3000-1:6000 births. These estimates are based on extrapolations of limited populations that have been screened using fluorescent in situ hybridization (FISH) technology. Males and females are equally affected, and there is no population "founder" effect. The deletion arises de novo frequently in all populations, and there is no reason to believe that the syndrome is more frequent in any particular ethnic background. The existing data do not yet take into account the rising prevalence due to increasing numbers of affected adults having their own affected children. Since this is a haplosufficiency disorder, one-half of the children of affected adults will have the deletion. Therefore, the prevalence is anticipated to rise over time. Currently, the figures are 6%-10% of new cases are familial. Since survival with cardiac anomalies was low until the mid-1980s, the familial cases are expected to rise. Moreover, within the Children's Hospital of Philadelphia (CHOP) cohort, the familial rate for patients with an atypical deletion such as the "B-D" deletion is much higher (5/11 or 45%), suggesting that those patients with a seemingly milder phenotype are more likely to reproduce.

Recent studies using SNP arrays have suggested that there are atypical deletions not detected by FISH-based strategies, and the true prevalence may be higher than suspected when these variants are included (see below). Commercial laboratories have reported classical deletions in approximately 1:100-1:200 samples sent for SNP array testing, and atypical deletions with approximately half of that frequency (Lisa Shaffer, Signature Genomics, personal communication). These laboratory sets represent patient cohorts with underlying medical problems but give valuable information on the relative frequencies of the typical and atypical deletions. Many of the atypical deletions would not have been identified with FISH technology, leading to the belief that we currently underascertain patients with the deletion.

While the frequency in the general population is slightly less frequent than trisomy 21, it is still sufficiently common that chromosome 22q11.2 deletion can occur in combination with other diagnoses. We have seen patients with Marfan syndrome and chromosome 22q11.2 deletion syndrome, Ehlers-Danlos and chromosome 22q11.2 deletion syndrome, and trisomy 21 and chromosome 22q11.2 deletion syndrome. There have also been distant family members with the deletion where it arose on completely distinct haplotypes and therefore represent distinct de novo events.

An important clinical aspect in the consideration of the demographic characteristics of the deletion is the frequency in unselected populations with compatible phenotypic features. The variability of the phenotypic features has made it difficult to define the exact clinical scenario where testing is warranted. Various algorithms have been developed to identify patient groups for whom testing for the deletion is clearly clinically warranted. These algorithms have thus far been disappointing at identifying patients outside of the most classic phenotype. Nevertheless, multiple studies have identified the frequency of the deletion in specific patient groups, and these data provide valuable context when considering the diagnostic approach. <ref>McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </ref>

==References==
{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome epidemiology and demographics

2020-08-28T00:19:57Z

Ayushijain: /* Incidence and Prevalence */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
<br />

==Epidemiology and Demographics==
The estimated prevalence has been cited in several studies as being 1:3000-1:6000 births. These estimates are based on extrapolations of limited populations that have been screened using fluorescent in situ hybridization (FISH) technology. Males and females are equally affected, and there is no population "founder" effect. The deletion arises de novo frequently in all populations, and there is no reason to believe that the syndrome is more frequent in any particular ethnic background. The existing data do not yet take into account the rising prevalence due to increasing numbers of affected adults having their own affected children. Since this is a haplosufficiency disorder, one-half of the children of affected adults will have the deletion. Therefore, the prevalence is anticipated to rise over time. Currently, the figures are 6%-10% of new cases are familial. Since survival with cardiac anomalies was low until the mid-1980s, the familial cases are expected to rise. Moreover, within the Children's Hospital of Philadelphia (CHOP) cohort, the familial rate for patients with an atypical deletion such as the "B-D" deletion is much higher (5/11 or 45%), suggesting that those patients with a seemingly milder phenotype are more likely to reproduce.

Recent studies using SNP arrays have suggested that there are atypical deletions not detected by FISH-based strategies, and the true prevalence may be higher than suspected when these variants are included (see below). Commercial laboratories have reported classical deletions in approximately 1:100-1:200 samples sent for SNP array testing, and atypical deletions with approximately half of that frequency (Lisa Shaffer, Signature Genomics, personal communication). These laboratory sets represent patient cohorts with underlying medical problems but give valuable information on the relative frequencies of the typical and atypical deletions. Many of the atypical deletions would not have been identified with FISH technology, leading to the belief that we currently underascertain patients with the deletion.

While the frequency in the general population is slightly less frequent than trisomy 21, it is still sufficiently common that chromosome 22q11.2 deletion can occur in combination with other diagnoses. We have seen patients with Marfan syndrome and chromosome 22q11.2 deletion syndrome, Ehlers-Danlos and chromosome 22q11.2 deletion syndrome, and trisomy 21 and chromosome 22q11.2 deletion syndrome. There have also been distant family members with the deletion where it arose on completely distinct haplotypes and therefore represent distinct de novo events.

An important clinical aspect in the consideration of the demographic characteristics of the deletion is the frequency in unselected populations with compatible phenotypic features. The variability of the phenotypic features has made it difficult to define the exact clinical scenario where testing is warranted. Various algorithms have been developed to identify patient groups for whom testing for the deletion is clearly clinically warranted. These algorithms have thus far been disappointing at identifying patients outside of the most classic phenotype. Nevertheless, multiple studies have identified the frequency of the deletion in specific patient groups, and these data provide valuable context when considering the diagnostic approach (

==References==
{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome causes

2020-08-28T00:04:22Z

Ayushijain: /* Overview */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands.

==Causes==
Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS. Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models.

Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands.

Mouse and zebrafish TBX1 knockout models have been studied to understand the embryologic basis of this disease. In mice, for instance, the absence of TBX1 causes severe pharyngeal, cardiac, thymic, and parathyroid defects as well as a behavioral disturbance.<ref>Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006 Sep;133(18):3587-95.</ref> Moreover, zebrafish knockouts have demonstrated defects in the thymus and pharyngeal arches as well as malformation of the ears and thymus.<ref> Guner-Ataman B, González-Rosa JM, Shah HN, Butty VL, Jeffrey S, Abrial M, Boyer LA, Burns CG, Burns CE. Failed Progenitor Specification Underlies the Cardiopharyngeal Phenotypes in a Zebrafish Model of 22q11.2 Deletion Syndrome. Cell Rep. 2018 Jul 31;24(5):1342-1354.e5.</ref>

TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the [[behavioral and developmental abnormalities]] seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome causes

2020-08-28T00:02:56Z

Ayushijain: /* Causes */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Causes==
Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS. TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands. Mouse and zebrafish TBX1 knockout models have been studied to understand the embryologic basis of this disease. In mice, for instance, the absence of TBX1 causes severe pharyngeal, cardiac, thymic, and parathyroid defects as well as a behavioral disturbance.<ref>Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006 Sep;133(18):3587-95.</ref> Moreover, zebrafish knockouts have demonstrated defects in the thymus and pharyngeal arches as well as malformation of the ears and thymus.<ref> Guner-Ataman B, González-Rosa JM, Shah HN, Butty VL, Jeffrey S, Abrial M, Boyer LA, Burns CG, Burns CE. Failed Progenitor Specification Underlies the Cardiopharyngeal Phenotypes in a Zebrafish Model of 22q11.2 Deletion Syndrome. Cell Rep. 2018 Jul 31;24(5):1342-1354.e5.</ref>

Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the [[behavioral and developmental abnormalities]] seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome causes

2020-08-28T00:01:05Z

Ayushijain: /* Causes */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Causes==
On a genetic basis, TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands. Mouse and zebrafish TBX1 knockout models have been studied to understand the embryologic basis of this disease. In mice, for instance, the absence of TBX1 causes severe pharyngeal, cardiac, thymic, and parathyroid defects as well as a behavioral disturbance.<ref>Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006 Sep;133(18):3587-95.</ref> Moreover, zebrafish knockouts have demonstrated defects in the thymus and pharyngeal arches as well as malformation of the ears and thymus.<ref> Guner-Ataman B, González-Rosa JM, Shah HN, Butty VL, Jeffrey S, Abrial M, Boyer LA, Burns CG, Burns CE. Failed Progenitor Specification Underlies the Cardiopharyngeal Phenotypes in a Zebrafish Model of 22q11.2 Deletion Syndrome. Cell Rep. 2018 Jul 31;24(5):1342-1354.e5.</ref>

Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS.[1] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the [[behavioral and developmental abnormalities]] seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome causes

2020-08-27T23:59:49Z

Ayushijain: /* Causes */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Causes==
On a genetic basis, TBX1 has correlations with the most prominent phenotypes characteristic of DGS. Failure in embryologic development of the pharyngeal pouches, which is driven by TBX1, leads to absence or hypoplasia of the thymus and parathyroid glands. Mouse and zebrafish TBX1 knockout models have been studied to understand the embryologic basis of this disease. In mice, for instance, the absence of TBX1 causes severe pharyngeal, cardiac, thymic, and parathyroid defects as well as a behavioral disturbance.Moreover, zebrafish knockouts have demonstrated defects in the thymus and pharyngeal arches as well as malformation of the ears and thymus.

Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS.[1] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the [[behavioral and developmental abnormalities]] seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome pathophysiology

2020-08-27T23:55:19Z

Ayushijain:

<div style="-webkit-user-select: none;">
{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
|-
|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
<br />
==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the '''velo-cardio-facial syndrome''' (also called '''Shprintzen's syndrome'''), '''DiGeorge syndrome''', '''hearing loss with craniofacial syndromes''' and '''conotruncal anomaly face syndrome''', thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym '''CATCH-22''' ('''C''' = cardiac defects, '''A''' = abnormal facies, '''T''' = thymic hypoplasia, '''C''' = cleft palate, '''H''' = hypocalcemia from parathyroid aplasia, '''22''' = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with [[Catch-22 (logic)|Catch-22]] meaning a 'no-win' situation.

In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

===Genetics===
[[Image:Autodominant.jpg|thumb|left|22q11.2 deletion syndrome is inherited in an [[autosomal dominant]] pattern.]]
Most people with 22q11.2 deletion syndrome are missing about 3 million [[base pair]]s (the building blocks of DNA) on one copy of [[chromosome 22 (human)|chromosome 22]] in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.

'''CAUSE OF DELETION'''

The deletion is bracketed by low copy number repeats (LCRs).Four discrete blocks of LCRs are found in this region and each block is comprised of multiple repeats. These blocks are named LCR A-D, with A being the most proximal (Figure 1). The deletion typically arises via unequal meiotic exchange, facilitated by asynchronous replication at the site of the deletion.The asynchronous replication can be associated with mispairing of the LCR and subsequent unequal crossing over. This mechanism predicts that duplications and deletions would be found in equal numbers. The characteristic deletion of chromosome 22q11.2 is at least 10 times more common than the next most frequent human deletion syndrome, suggesting that these repeat blocks are inherently unstable.The LCRs on chromosome 22q11.2 are larger and more complex and have higher homology than any of the other LCRs in the genome associated with human chromosomal deletion syndromes.<ref> McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </ref>

The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.

DiGeorge syndrome causes migration defects of [[neural crest]]-derived tissues, particularly affecting development of the third and fourth [[Branchial pouches]] (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this etiology.

Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

===Associated Disorders===

*[[Congenital heart disease]] (74% of individuals), particularly conotruncal malformations ([[tetralogy of Fallot]], [[interrupted aortic arch]], [[ventricular septal defect]], and [[persistent truncus arteriosus]])
*[[Immune deficiency]]
*[[Renal]] anomalies (37%)
*[[Autoimmune disorders]]
*[[Autism]] and [[Autism spectrum disorders]]

[[Thymus]], [[parathyroid gland]]s and [[heart]] derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to [[yeast infections]].
[[Category:Hematology]]
==References==
{{Reflist|2}}

{{WH}}
{{WS}}

]

22q11.2 deletion syndrome pathophysiology

2020-08-27T23:53:05Z

Ayushijain: /* Pathophysiology */

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|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
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__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
<br />
==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the '''velo-cardio-facial syndrome''' (also called '''Shprintzen's syndrome'''), '''DiGeorge syndrome''', '''hearing loss with craniofacial syndromes''' and '''conotruncal anomaly face syndrome''', thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym '''CATCH-22''' ('''C''' = cardiac defects, '''A''' = abnormal facies, '''T''' = thymic hypoplasia, '''C''' = cleft palate, '''H''' = hypocalcemia from parathyroid aplasia, '''22''' = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with [[Catch-22 (logic)|Catch-22]] meaning a 'no-win' situation.

In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

===Genetics===
[[Image:Autodominant.jpg|thumb|left|22q11.2 deletion syndrome is inherited in an [[autosomal dominant]] pattern.]]
Most people with 22q11.2 deletion syndrome are missing about 3 million [[base pair]]s (the building blocks of DNA) on one copy of [[chromosome 22 (human)|chromosome 22]] in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.

'''CAUSE OF DELETION'''

The deletion is bracketed by low copy number repeats (LCRs).Four discrete blocks of LCRs are found in this region and each block is comprised of multiple repeats. These blocks are named LCR A-D, with A being the most proximal (Figure 1). The deletion typically arises via unequal meiotic exchange, facilitated by asynchronous replication at the site of the deletion.The asynchronous replication can be associated with mispairing of the LCR and subsequent unequal crossing over. This mechanism predicts that duplications and deletions would be found in equal numbers. The characteristic deletion of chromosome 22q11.2 is at least 10 times more common than the next most frequent human deletion syndrome, suggesting that these repeat blocks are inherently unstable.The LCRs on chromosome 22q11.2 are larger and more complex and have higher homology than any of the other LCRs in the genome associated with human chromosomal deletion syndromes.<ref> McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </ref>

The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.

DiGeorge syndrome causes migration defects of [[neural crest]]-derived tissues, particularly affecting development of the third and fourth [[Branchial pouches]] (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this etiology.

Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

===Associated Disorders===

*[[Congenital heart disease]] (74% of individuals), particularly conotruncal malformations ([[tetralogy of Fallot]], [[interrupted aortic arch]], [[ventricular septal defect]], and [[persistent truncus arteriosus]])
*[[Immune deficiency]]
*[[Renal]] anomalies (37%)
*[[Autoimmune disorders]]
*[[Autism]] and [[Autism spectrum disorders]]

[[Thymus]], [[parathyroid gland]]s and [[heart]] derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to [[yeast infections]].
[[Category:Hematology]]
==References==
{{Reflist|2}}

{{WH}}
{{WS}}

]

22q11.2 deletion syndrome pathophysiology

2020-08-27T23:29:27Z

Ayushijain:

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{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
|-
|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
<br />
==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the '''velo-cardio-facial syndrome''' (also called '''Shprintzen's syndrome'''), '''DiGeorge syndrome''', '''hearing loss with craniofacial syndromes''' and '''conotruncal anomaly face syndrome''', thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym '''CATCH-22''' ('''C''' = cardiac defects, '''A''' = abnormal facies, '''T''' = thymic hypoplasia, '''C''' = cleft palate, '''H''' = hypocalcemia from parathyroid aplasia, '''22''' = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with [[Catch-22 (logic)|Catch-22]] meaning a 'no-win' situation.

In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

'''CAUSE OF DELETION'''

The deletion is bracketed by low copy number repeats (LCRs).Four discrete blocks of LCRs are found in this region and each block is comprised of multiple repeats. These blocks are named LCR A-D, with A being the most proximal (Figure 1). The deletion typically arises via unequal meiotic exchange, facilitated by asynchronous replication at the site of the deletion.The asynchronous replication can be associated with mispairing of the LCR and subsequent unequal crossing over. This mechanism predicts that duplications and deletions would be found in equal numbers. The characteristic deletion of chromosome 22q11.2 is at least 10 times more common than the next most frequent human deletion syndrome, suggesting that these repeat blocks are inherently unstable.The LCRs on chromosome 22q11.2 are larger and more complex and have higher homology than any of the other LCRs in the genome associated with human chromosomal deletion syndromes.<REF> McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </REF>

The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.

DiGeorge syndrome causes migration defects of [[neural crest]]-derived tissues, particularly affecting development of the third and fourth [[Branchial pouches]] (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this etiology.

===Genetics===
[[Image:Autodominant.jpg|thumb|left|22q11.2 deletion syndrome is inherited in an [[autosomal dominant]] pattern.]]
Most people with 22q11.2 deletion syndrome are missing about 3 million [[base pair]]s (the building blocks of DNA) on one copy of [[chromosome 22 (human)|chromosome 22]] in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.

Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

===Associated Disorders===

*[[Congenital heart disease]] (74% of individuals), particularly conotruncal malformations ([[tetralogy of Fallot]], [[interrupted aortic arch]], [[ventricular septal defect]], and [[persistent truncus arteriosus]])
*[[Immune deficiency]]
*[[Renal]] anomalies (37%)
*[[Autoimmune disorders]]
*[[Autism]] and [[Autism spectrum disorders]]

[[Thymus]], [[parathyroid gland]]s and [[heart]] derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to [[yeast infections]].
[[Category:Hematology]]
==References==
{{Reflist|2}}

{{WH}}
{{WS}}

]

22q11.2 deletion syndrome pathophysiology

2020-08-27T23:27:39Z

Ayushijain:

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{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
|-
|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.
<br />
==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the '''velo-cardio-facial syndrome''' (also called '''Shprintzen's syndrome'''), '''DiGeorge syndrome''', '''hearing loss with craniofacial syndromes''' and '''conotruncal anomaly face syndrome''', thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym '''CATCH-22''' ('''C''' = cardiac defects, '''A''' = abnormal facies, '''T''' = thymic hypoplasia, '''C''' = cleft palate, '''H''' = hypocalcemia from parathyroid aplasia, '''22''' = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with [[Catch-22 (logic)|Catch-22]] meaning a 'no-win' situation.

In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

'''CAUSE OF DELETION'''

The deletion is bracketed by low copy number repeats (LCRs).Four discrete blocks of LCRs are found in this region and each block is comprised of multiple repeats. These blocks are named LCR A-D, with A being the most proximal (Figure 1). The deletion typically arises via unequal meiotic exchange, facilitated by asynchronous replication at the site of the deletion.The asynchronous replication can be associated with mispairing of the LCR and subsequent unequal crossing over. This mechanism predicts that duplications and deletions would be found in equal numbers. The characteristic deletion of chromosome 22q11.2 is at least 10 times more common than the next most frequent human deletion syndrome, suggesting that these repeat blocks are inherently unstable.The LCRs on chromosome 22q11.2 are larger and more complex and have higher homology than any of the other LCRs in the genome associated with human chromosomal deletion syndromes.

The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.

DiGeorge syndrome causes migration defects of [[neural crest]]-derived tissues, particularly affecting development of the third and fourth [[Branchial pouches]] (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this etiology.

===Genetics===
[[Image:Autodominant.jpg|thumb|left|22q11.2 deletion syndrome is inherited in an [[autosomal dominant]] pattern.]]
Most people with 22q11.2 deletion syndrome are missing about 3 million [[base pair]]s (the building blocks of DNA) on one copy of [[chromosome 22 (human)|chromosome 22]] in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.

Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

===Associated Disorders===

*[[Congenital heart disease]] (74% of individuals), particularly conotruncal malformations ([[tetralogy of Fallot]], [[interrupted aortic arch]], [[ventricular septal defect]], and [[persistent truncus arteriosus]])
*[[Immune deficiency]]
*[[Renal]] anomalies (37%)
*[[Autoimmune disorders]]
*[[Autism]] and [[Autism spectrum disorders]]

[[Thymus]], [[parathyroid gland]]s and [[heart]] derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to [[yeast infections]].
[[Category:Hematology]]
==References==
{{Reflist|2}}

{{WH}}
{{WS}}

]

File:Original.00005792-201101000-00001.F1-1.jpg

2020-08-27T23:25:14Z

Ayushijain:

The genes within the commonly deleted region of chromosome 22. The smaller boxes represent the genes within the commonly deleted region. The larger boxes below the schematic chromosome represent the LCRs. The most common deletion, which is 3Mb, is seen in approximately 70%-80% of patients and occurs between the 2 most distant LCRs. Fifteen to 30% of patients have a slightly smaller 1.5 Mb deletion, and the remainder of patients have a variety of deletions with 1 breakpoint in an LCR.

22q11.2 deletion syndrome overview

2020-08-27T23:14:42Z

Ayushijain:

<div style="-webkit-user-select: none;">
{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
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|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
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__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==

'''22q11.2 deletion syndrome''' is a disorder caused by the deletion of a small part of [[chromosome 22 (human)|chromosome 22]]. It occurs in approximately 1:4000 births.<ref> McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </ref>

The deletion occurs near the middle of the [[chromosome]] at a location designated q11.2.
DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused by defects in the development of structures derived from the pharyngeal arches during embryogenesis. Key findings comprises of [[thymic hypoplasia]], [[hypocalcaemia,]] outflow tract defects of the heart, and dysmorphic facies.
The manifestations of this syndrome cross all medical specialties, and care of the children and adults can be complex. Many patients have a mild to moderate immune deficiency, and the majority of patients have a cardiac anomaly. Additional features include renal anomalies, eye anomalies, hypoparathyroidism, skeletal defects, and developmental delay. Each child's needs must be tailored to his or her specific medical problems, and as the child transitions to adulthood, additional issues will arise. A holistic approach, addressing medical and behavioral needs, can be very helpful.
<ref>McDonald-McGinn, Donna M. MS, CGC; Sullivan, Kathleen E. MD, PhD Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), Medicine: January 2011 - Volume 90 - Issue 1 - p 1-18
doi: 10.1097/MD.0b013e3182060469 </ref>

==Historical Perspective==
DGS characteristics were first described in 1828 but adequately reported later in 1965 by Dr. Angelo DiGeorge, as a clinical trial that included immunodeficiency, hypoparathyroidism, and congenital heart disease.

Historically, DGS was grouped within a sphere of other syndromes such as Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS, collectively called '''22q11 deletion syndromes'''. They have the same genetic etiology but their varying phenotypes has has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.

==Classification==
There is no established system for the classification of DGS.

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

==Causes==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Differentiating [Disease] from Other Diseases==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.<br />
==Epidemiology and Demographics==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Risk Factors==
The only known risk factor is that of a family history of DGS.

==Screening==
Screening of DGS depends on known family history and then approaching with genetic studies in individual cases.

==Natural History, Complications, and Prognosis==
===Natural History===
It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features.

===Complications===
Most patients with DGS may progress to develop severe recurrent infections, autoimmune diseases, and hematologic malignancies.

===Prognosis===
Prognosis is very poor, if left untreated, most patients die by 12 months of age.

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.

Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a [[cleft palate]] or other defect in the palate), [[autism]], other [[Learning disability|learning disabilities]], mild differences in facial features, and recurrent viral or fungal [[Infection|infections]] are common due to problems with the [[immune system]]'s T-cell mediated response.

===Physical Examination===
A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent with aortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.

Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia

Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.

Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.

===Laboratory Findings===

*[[Hypocalcemia]] (50%)(due to hypoparathyroidism)
*[[Growth hormone]] deficiency

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}
<references />

22q11.2 deletion syndrome overview

2020-08-27T23:10:38Z

Ayushijain: /* Overview */

<div style="-webkit-user-select: none;">
{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
|-
|{{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==

'''22q11.2 deletion syndrome''' is a disorder caused by the deletion of a small part of [[chromosome 22 (human)|chromosome 22]]. It occurs in approximately 1:4000 births.

The deletion occurs near the middle of the [[chromosome]] at a location designated q11.2.

DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused by defects in the development of structures derived from the pharyngeal arches during embryogenesis. Key findings comprises of [[thymic hypoplasia]], [[hypocalcaemia,]] outflow tract defects of the heart, and dysmorphic facies.

==Historical Perspective==
DGS characteristics were first described in 1828 but adequately reported later in 1965 by Dr. Angelo DiGeorge, as a clinical trial that included immunodeficiency, hypoparathyroidism, and congenital heart disease.

Historically, DGS was grouped within a sphere of other syndromes such as Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS, collectively called '''22q11 deletion syndromes'''. They have the same genetic etiology but their varying phenotypes has has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.

==Classification==
There is no established system for the classification of DGS.

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

==Causes==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Differentiating [Disease] from Other Diseases==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.<br />
==Epidemiology and Demographics==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Risk Factors==
The only known risk factor is that of a family history of DGS.

==Screening==
Screening of DGS depends on known family history and then approaching with genetic studies in individual cases.

==Natural History, Complications, and Prognosis==
===Natural History===
It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features.

===Complications===
Most patients with DGS may progress to develop severe recurrent infections, autoimmune diseases, and hematologic malignancies.

===Prognosis===
Prognosis is very poor, if left untreated, most patients die by 12 months of age.

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.

Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a [[cleft palate]] or other defect in the palate), [[autism]], other [[Learning disability|learning disabilities]], mild differences in facial features, and recurrent viral or fungal [[Infection|infections]] are common due to problems with the [[immune system]]'s T-cell mediated response.

===Physical Examination===
A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent with aortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.

Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia

Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.

Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.

===Laboratory Findings===

*[[Hypocalcemia]] (50%)(due to hypoparathyroidism)
*[[Growth hormone]] deficiency

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}
<references />

22q11.2 deletion syndrome

2020-08-27T23:02:38Z

Ayushijain:

__NOTOC__
{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = |
Caption = |
DiseasesDB = 3631 |
ICD10 = {{ICD10|D|82|1|d|80}} |
ICD9 = {{ICD9|279.11}}, {{ICD9|758.32}} |
ICDO = |
OMIM = 188400 |
MedlinePlus = |
MeshID = D004062 |
}}
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

{{SK}} DiGeorge syndrome; Velocardiofacial syndrome; Di George syndrome; Strong syndrome; third and fourth pharyngeal arch syndrome of Di George; CATCH phenotype; conotruncal anomaly face syndrome

==[[22q11.2 deletion syndrome overview|Overview]]==

==[[22q11.2 deletion syndrome historical perspective|Historical Perspective]]==

==[[22q11.2 deletion syndrome classification|Classification]]==

==[[22q11.2 deletion syndrome pathophysiology|Pathophysiology]]==

==[[22q11.2 deletion syndrome differential diagnosis|Differentiating 22q11.2 deletion syndrome from other Diseases]]==

==[[22q11.2 deletion syndrome causes|Causes]]==

==[[22q11.2 deletion syndrome epidemiology and demographics|Epidemiology and Demographics]]==

==[[22q11.2 deletion syndrome risk factors|Risk Factors]]==

==[[22q11.2 deletion syndrome screening|Screening]]==

==[[22q11.2 deletion syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]==

==Diagnosis==
[[22q11.2 deletion syndrome history and symptoms|History and Symptoms ]] | [[ 22q11.2 deletion syndrome physical examination|Physical Examination]] | [[22q11.2 deletion syndrome laboratory findings|Laboratory Findings]] | [[22q11.2 deletion syndrome electrocardiogram|Electrocardiogram]] | [[22q11.2 deletion syndrome chest x ray|Chest X Ray]] | [[22q11.2 deletion syndrome CT|CT ]] | [[22q11.2 deletion syndrome MRI|MRI]] | [[22q11.2 deletion syndrome echocardiography|Echocardiography]] | [[22q11.2 deletion syndrome other imaging findings|Other Imaging Findings]] | [[22q11.2 deletion syndrome other diagnostic studies|Other Diagnostic Studies]]

==Treatment==
[[22q11.2 deletion syndrome medical therapy|Medical Therapy]] | [[22q11.2 deletion syndrome surgery |Surgery]] | [[22q11.2 deletion syndrome primary prevention|Primary Prevention]] | [[22q11.2 deletion syndrome secondary prevention|Secondary Prevention]] | [[22q11.2 deletion syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[22q11.2 deletion syndrome future or investigational therapies|Future or Investigational Therapies]]

22q11.2 deletion syndrome surgery

2020-08-25T18:26:12Z

Ayushijain: /* Surgery */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
Surgical options depends on the presenting symptom at the time of diagnosis and can vary from cardiac sugery to a simple Cleft palate surgery. Thymic Transplantation becomes an obvious choice in a complete DGS case.

==Surgery==

* Patients with 22q11.2 deletion syndrome may undergo [[cardiac surgery]] for their heart abnormalities.

* Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
* Thymic transplantations is preferred in complete DGS .

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome medical therapy

2020-08-25T18:22:26Z

Ayushijain: /* Overview */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunization with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing [[hypocalcemia]] is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete [[DiGeorge syndrome]].

==Medical Therapy==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunization with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing [[hypocalcemia]] is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete [[DiGeorge syndrome]].<ref>{{cite journal |author=Markert ML, Devlin BH, Alexieff MJ, ''et al'' |title=Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants |journal=Blood |volume=109 |issue=10 |pages=4539-47 |year=2007 |pmid=17284531 |doi=10.1182/blood-2006-10-048652}}</ref>

*Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG, antibiotic prophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
*Immunization, boosters, intravenous immunoglobulin, and antibiotic prophylaxis regimens should revolve around the individual patient's laboratory values. Antibody titer to administered vaccines should be re-evaluated every six to twelve months to determine the necessity of re-vaccination.Controversy exists surrounding the administration of live vaccines, including the MMR, oral polio, and rotavirus vaccines. However, current evidence suggests both safety and efficacy in children older than one year with proven vaccine response, CD8 count greater than 300, and CD4 count greater than 500. Rotavirus vaccination, of note, has been associated with diarrheal illness in patients with SCID and should not be administered to infants with reduced T cell counts.<ref> Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J. Allergy Clin. Immunol. 2010 Oct;126(4):868-9.</ref> <ref>Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010 Sep 14;28(40):6609-12.</ref>
*Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
*Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
*Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
*Autoimmune diseases are common in DGS patients, including immune thrombocytopenia (ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patients should be evaluated carefully for autoimmune symptoms regularly.
*Audiologic evaluation is necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
*Early intervention services are beneficial for children with impaired cognitive and behavioral development.
*Speech therapy is necessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
*Psychiatric care for DGS patients with depressive and psychotic symptoms is necessary, as diseases like schizophrenia are associated with DGS.<ref>Sumitomo A, Horike K, Hirai K, Butcher N, Boot E, Sakurai T, Nucifora FC, Bassett AS, Sawa A, Tomoda T. A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson's disease and schizophrenia. Sci Adv. 2018 Aug;4(8):eaar6637.</ref> <ref> Meechan DW, Maynard TM, Tucker ES, Fernandez A, Karpinski BA, Rothblat LA, LaMantia AS. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog. Neurobiol. 2015 Jul;130:1-28.</ref>
*Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.

'''''Advanced approaches for the management of children with complete DiGeorge anomaly'''''

In the cDGS featuring no thymus function and bone marrow stem cells can not develop into T cells, children usually die by age 2 years due to severe infections. In this setting, the proposal is to T cell–replete HSCT. Nevertheless, because of the absence of thymus, this strategy can only obtain engraftment of post thymic T cells.<ref>McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol. Res. 2009;45(1):37-45. </ref> A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.<ref>Janda A, Sedlacek P, Hönig M, Friedrich W, Champagne M, Matsumoto T, Fischer A, Neven B, Contet A, Bensoussan D, Bordigoni P, Loeb D, Savage W, Jabado N, Bonilla FA, Slatter MA, Davies EG, Gennery AR. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010 Sep 30;116(13):2229-36.</ref> Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producing naive T cells with a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicate up to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.<ref>Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ. Thymus transplantation for complete DiGeorge syndrome: European experience. J. Allergy Clin. Immunol. 2017 Dec;140(6):1660-1670.e16.</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome medical therapy

2020-08-25T18:21:53Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==

==Medical Therapy==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunization with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing [[hypocalcemia]] is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete [[DiGeorge syndrome]].<ref>{{cite journal |author=Markert ML, Devlin BH, Alexieff MJ, ''et al'' |title=Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants |journal=Blood |volume=109 |issue=10 |pages=4539-47 |year=2007 |pmid=17284531 |doi=10.1182/blood-2006-10-048652}}</ref>

*Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG, antibiotic prophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
*Immunization, boosters, intravenous immunoglobulin, and antibiotic prophylaxis regimens should revolve around the individual patient's laboratory values. Antibody titer to administered vaccines should be re-evaluated every six to twelve months to determine the necessity of re-vaccination.Controversy exists surrounding the administration of live vaccines, including the MMR, oral polio, and rotavirus vaccines. However, current evidence suggests both safety and efficacy in children older than one year with proven vaccine response, CD8 count greater than 300, and CD4 count greater than 500. Rotavirus vaccination, of note, has been associated with diarrheal illness in patients with SCID and should not be administered to infants with reduced T cell counts.<ref> Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J. Allergy Clin. Immunol. 2010 Oct;126(4):868-9.</ref> <ref>Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010 Sep 14;28(40):6609-12.</ref>
*Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
*Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
*Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
*Autoimmune diseases are common in DGS patients, including immune thrombocytopenia (ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patients should be evaluated carefully for autoimmune symptoms regularly.
*Audiologic evaluation is necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
*Early intervention services are beneficial for children with impaired cognitive and behavioral development.
*Speech therapy is necessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
*Psychiatric care for DGS patients with depressive and psychotic symptoms is necessary, as diseases like schizophrenia are associated with DGS.<ref>Sumitomo A, Horike K, Hirai K, Butcher N, Boot E, Sakurai T, Nucifora FC, Bassett AS, Sawa A, Tomoda T. A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson's disease and schizophrenia. Sci Adv. 2018 Aug;4(8):eaar6637.</ref> <ref> Meechan DW, Maynard TM, Tucker ES, Fernandez A, Karpinski BA, Rothblat LA, LaMantia AS. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog. Neurobiol. 2015 Jul;130:1-28.</ref>
*Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.

'''''Advanced approaches for the management of children with complete DiGeorge anomaly'''''

In the cDGS featuring no thymus function and bone marrow stem cells can not develop into T cells, children usually die by age 2 years due to severe infections. In this setting, the proposal is to T cell–replete HSCT. Nevertheless, because of the absence of thymus, this strategy can only obtain engraftment of post thymic T cells.<ref>McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol. Res. 2009;45(1):37-45. </ref> A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.<ref>Janda A, Sedlacek P, Hönig M, Friedrich W, Champagne M, Matsumoto T, Fischer A, Neven B, Contet A, Bensoussan D, Bordigoni P, Loeb D, Savage W, Jabado N, Bonilla FA, Slatter MA, Davies EG, Gennery AR. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010 Sep 30;116(13):2229-36.</ref> Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producing naive T cells with a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicate up to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.<ref>Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ. Thymus transplantation for complete DiGeorge syndrome: European experience. J. Allergy Clin. Immunol. 2017 Dec;140(6):1660-1670.e16.</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome medical therapy

2020-08-25T18:19:54Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==

==Medical Therapy==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunisation with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing hypocalcaemia is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete DiGeorge syndrome.<ref>{{cite journal |author=Markert ML, Devlin BH, Alexieff MJ, ''et al'' |title=Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants |journal=Blood |volume=109 |issue=10 |pages=4539-47 |year=2007 |pmid=17284531 |doi=10.1182/blood-2006-10-048652}}</ref>

Treatment and management of DGS require intensive interprofessional care:

* Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG, antibiotic prophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
* Immunization, boosters, intravenous immunoglobulin, and antibiotic prophylaxis regimens should revolve around the individual patient's laboratory values. Antibody titer to administered vaccines should be re-evaluated every six to twelve months to determine the necessity of re-vaccination.Controversy exists surrounding the administration of live vaccines, including the MMR, oral polio, and rotavirus vaccines. However, current evidence suggests both safety and efficacy in children older than one year with proven vaccine response, CD8 count greater than 300, and CD4 count greater than 500. Rotavirus vaccination, of note, has been associated with diarrheal illness in patients with SCID and should not be administered to infants with reduced T cell counts.<ref> Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J. Allergy Clin. Immunol. 2010 Oct;126(4):868-9.</ref> <ref>Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010 Sep 14;28(40):6609-12.</ref>
* Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
* Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
* Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
* Autoimmune diseases are common in DGS patients, including immune thrombocytopenia (ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patients should be evaluated carefully for autoimmune symptoms regularly.
* Audiologic evaluation is necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
* Early intervention services are beneficial for children with impaired cognitive and behavioral development.
* Speech therapy is necessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
* Psychiatric care for DGS patients with depressive and psychotic symptoms is necessary, as diseases like schizophrenia are associated with DGS.<ref>Sumitomo A, Horike K, Hirai K, Butcher N, Boot E, Sakurai T, Nucifora FC, Bassett AS, Sawa A, Tomoda T. A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson's disease and schizophrenia. Sci Adv. 2018 Aug;4(8):eaar6637.</ref> <ref> Meechan DW, Maynard TM, Tucker ES, Fernandez A, Karpinski BA, Rothblat LA, LaMantia AS. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog. Neurobiol. 2015 Jul;130:1-28.</ref>
* Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.

''Advanced approaches for the management of children with complete DiGeorge anomaly''

In the cDGS featuring no thymus function and bone marrow stem cells can not develop into T cells, children usually die by age 2 years due to severe infections. In this setting, the proposal is to T cell–replete HSCT. Nevertheless, because of the absence of thymus, this strategy can only obtain engraftment of post thymic T cells.<ref>McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol. Res. 2009;45(1):37-45. </ref> A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.<ref>Janda A, Sedlacek P, Hönig M, Friedrich W, Champagne M, Matsumoto T, Fischer A, Neven B, Contet A, Bensoussan D, Bordigoni P, Loeb D, Savage W, Jabado N, Bonilla FA, Slatter MA, Davies EG, Gennery AR. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010 Sep 30;116(13):2229-36.</ref> Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producing naive T cells with a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicate up to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.<ref>Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ. Thymus transplantation for complete DiGeorge syndrome: European experience. J. Allergy Clin. Immunol. 2017 Dec;140(6):1660-1670.e16.</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome medical therapy

2020-08-25T18:19:29Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==

==Medical Therapy==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunisation with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing hypocalcaemia is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete DiGeorge syndrome.<ref>{{cite journal |author=Markert ML, Devlin BH, Alexieff MJ, ''et al'' |title=Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants |journal=Blood |volume=109 |issue=10 |pages=4539-47 |year=2007 |pmid=17284531 |doi=10.1182/blood-2006-10-048652}}</ref>

Treatment and management of DGS require intensive interprofessional care:

* Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG, antibiotic prophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
* Immunization, boosters, intravenous immunoglobulin, and antibiotic prophylaxis regimens should revolve around the individual patient's laboratory values. Antibody titer to administered vaccines should be re-evaluated every six to twelve months to determine the necessity of re-vaccination.Controversy exists surrounding the administration of live vaccines, including the MMR, oral polio, and rotavirus vaccines. However, current evidence suggests both safety and efficacy in children older than one year with proven vaccine response, CD8 count greater than 300, and CD4 count greater than 500. Rotavirus vaccination, of note, has been associated with diarrheal illness in patients with SCID and should not be administered to infants with reduced T cell counts.<ref> Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J. Allergy Clin. Immunol. 2010 Oct;126(4):868-9.</ref> <ref>Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010 Sep 14;28(40):6609-12.</ref>
* Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
* Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
* Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
* Autoimmune diseases are common in DGS patients, including immune thrombocytopenia (ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patients should be evaluated carefully for autoimmune symptoms regularly.
* Audiologic evaluation is necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
* Early intervention services are beneficial for children with impaired cognitive and behavioral development.
* Speech therapy is necessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
* Psychiatric care for DGS patients with depressive and psychotic symptoms is necessary, as diseases like schizophrenia are associated with DGS.<ref>Sumitomo A, Horike K, Hirai K, Butcher N, Boot E, Sakurai T, Nucifora FC, Bassett AS, Sawa A, Tomoda T. A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson's disease and schizophrenia. Sci Adv. 2018 Aug;4(8):eaar6637.</ref> <ref> Meechan DW, Maynard TM, Tucker ES, Fernandez A, Karpinski BA, Rothblat LA, LaMantia AS. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog. Neurobiol. 2015 Jul;130:1-28.</ref>
* Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.

''Advanced approaches for the management of children with complete DiGeorge anomaly''

In the cDGS featuring no thymus function and bone marrow stem cells can not develop into T cells, children usually die by age 2 years due to severe infections. In this setting, the proposal is to T cell–replete HSCT. Nevertheless, because of the absence of thymus, this strategy can only obtain engraftment of post thymic T cells.<ref>McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol. Res. 2009;45(1):37-45. </ref> A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.<ref>Janda A, Sedlacek P, Hönig M, Friedrich W, Champagne M, Matsumoto T, Fischer A, Neven B, Contet A, Bensoussan D, Bordigoni P, Loeb D, Savage W, Jabado N, Bonilla FA, Slatter MA, Davies EG, Gennery AR. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010 Sep 30;116(13):2229-36.</ref> Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producing naive T cells with a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicate up to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.<ref>Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ. Thymus transplantation for complete DiGeorge syndrome: European experience. J. Allergy Clin. Immunol. 2017 Dec;140(6):1660-1670.e16.</ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome medical therapy

2020-08-25T18:15:24Z

Ayushijain: /* Medical Therapy */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==

==Medical Therapy==
Although genetic transplantation methods are currently being developed by researchers, there is yet no genetic treatment of this disease.

It is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunisation with live vaccines.

Treatment is largely symptomatic, [[infections]] are treated with [[antibiotics]]. [[Hypoparathyroidism]] causing hypocalcaemia is often transient, but may require lifelong vitamin D treatment.

Thymus transplantation can be used to address absence of the thymus in complete DiGeorge syndrome.<ref>{{cite journal |author=Markert ML, Devlin BH, Alexieff MJ, ''et al'' |title=Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants |journal=Blood |volume=109 |issue=10 |pages=4539-47 |year=2007 |pmid=17284531 |doi=10.1182/blood-2006-10-048652}}</ref>

Treatment and management of DGS require intensive interprofessional care:

* Fortunately, many patients with DGS have minor immunodeficiency, with preservation of T cell function despite decreased T cell production. Frequent follow-up with an immunologist experienced in treating primary immunodeficiencies is advisable. Immunodeficiency in neonates with complete DGS (cDGS) requires management with isolation, intravenous IgG, antibiotic prophylaxis, and either thymic or hematopoietic cell transplant (HSCT).
* Immunization, boosters, intravenous immunoglobulin, and antibiotic prophylaxis regimens should revolve around the individual patient's laboratory values. Antibody titer to administered vaccines should be re-evaluated every six to twelve months to determine the necessity of re-vaccination.Controversy exists surrounding the administration of live vaccines, including the MMR, oral polio, and rotavirus vaccines. However, current evidence suggests both safety and efficacy in children older than one year with proven vaccine response, CD8 count greater than 300, and CD4 count greater than 500. Rotavirus vaccination, of note, has been associated with diarrheal illness in patients with SCID and should not be administered to infants with reduced T cell counts.
* Cardiac anomalies, if not diagnosed during the fetal ultrasound, may present shortly after birth as life-threatening cyanotic heart disease. Pediatric cardiothoracic surgery evaluation may be urgently required. Blood products, if necessary, should be irradiated, CMV negative, and leukocyte reduced to prevent transfusion-associated graft-versus-host disease. These measures also aim to reduce lung injury, particularly in surgical cases requiring cardiopulmonary bypass.
* Cleft palate cases require evaluation by an otolaryngologist, plastic surgeon, or oral & maxillofacial surgeon with experience in surgical correction of palatal defects. Repair of a cleft palate can improve feeding ability, speech, and reduce the incidence of sinopulmonary infections.
* Hypocalcemia is manageable with calcium and vitamin D supplementation. Recombinant human PTH is an option in DGS patients refractory to standard therapy.
* Autoimmune diseases are common in DGS patients, including immune thrombocytopenia (ITP), rheumatoid arthritis, autoimmune hemolytic anemia, Graves disease, and Hashimoto thyroiditis. DGS patients should be evaluated carefully for autoimmune symptoms regularly.
* Audiologic evaluation is necessary for DGS patients experiencing difficulty with hearing. Children too young to express difficulty with hearing need assessment, particularly with a delay in cognitive and behavioral development.
* Early intervention services are beneficial for children with impaired cognitive and behavioral development.
* Speech therapy is necessary for difficulty with language secondary to craniofacial anomalies and/or cognitive impairment.
* Psychiatric care for DGS patients with depressive and psychotic symptoms is necessary, as diseases like schizophrenia are associated with DGS.
* Genetic counseling is a reasonable consideration for parents of a child with DGS who desire more children, as well as for patients with DGS who may want to become parents. If a parent has the same mutation as an affected child, there is a 50% chance a new baby will also have DGS.

''Advanced approaches for the management of children with complete DiGeorge anomaly''

In the cDGS featuring no thymus function and bone marrow stem cells can not develop into T cells, children usually die by age 2 years due to severe infections. In this setting, the proposal is to T cell–replete HSCT. Nevertheless, because of the absence of thymus, this strategy can only obtain engraftment of post thymic T cells. A multicenter survey on the outcome of HSCT showed a survival rate of 33% after matched unrelated donors and 60% in the case of matched sibling transplantations.Recently, the FDA approved the thymus transplantation as standard care. This approach focuses on producing naive T cells with a broad T-cell receptor set. The procedure takes place using general anesthesia, and thymus tissue usually gets transplanted into the recipient subject's quadriceps. Studies indicate up to 75% of long-term survival but have described frequent autoimmune sequelae (e.g., autoimmune hemolysis, thyroiditis, thrombocytopenia, enteropathy, and neutropenia) in survivors.

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome overview

2020-08-19T16:11:21Z

Ayushijain: /* Physical Examination */

<div style="-webkit-user-select: none;">
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
|-
| {{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==

'''22q11.2 deletion syndrome''' is a disorder caused by the deletion of a small piece of [[chromosome 22 (human)|chromosome 22]]. The deletion occurs near the middle of the [[chromosome]] at a location designated q11.2.
DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused by defects in the development of structures derived from the pharyngeal arches during embryogenesis.

It comprises of [[thymic hypoplasia]], [[hypocalcaemia,]] outflow tract defects of the heart, and dysmorphic facies.

==Historical Perspective==
DGS characteristics were first described in 1828 but adequately reported later in 1965 by Dr. Angelo DiGeorge, as a clinical trial that included immunodeficiency, hypoparathyroidism, and congenital heart disease.

Historically, DGS was grouped within a sphere of other syndromes such as Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS, collectively called '''22q11 deletion syndromes'''. They have the same genetic etiology but their varying phenotypes has has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.

==Classification==
There is no established system for the classification of DGS.

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

==Causes==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Differentiating [Disease] from Other Diseases==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.<br />
==Epidemiology and Demographics==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Risk Factors==
The only known risk factor is that of a family history of DGS.

==Screening==
Screening of DGS depends on known family history and then approaching with genetic studies in individual cases.

==Natural History, Complications, and Prognosis==
===Natural History ===
It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features.

===Complications===
Most patients with DGS may progress to develop severe recurrent infections, autoimmune diseases, and hematologic malignancies.

===Prognosis===
Prognosis is very poor, if left untreated, most patients die by 12 months of age.

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.

Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a [[cleft palate]] or other defect in the palate), [[autism]], other [[Learning disability|learning disabilities]], mild differences in facial features, and recurrent viral or fungal [[Infection|infections]] are common due to problems with the [[immune system]]'s T-cell mediated response.

===Physical Examination===
A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent with aortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.

Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia

Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.

Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.

===Laboratory Findings===

* [[Hypocalcemia]] (50%)(due to hypoparathyroidism)
* [[Growth hormone]] deficiency

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}
<references />

22q11.2 deletion syndrome overview

2020-08-19T16:07:06Z

Ayushijain: /* History and Symptoms */

<div style="-webkit-user-select: none;">
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
|-
| {{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==

'''22q11.2 deletion syndrome''' is a disorder caused by the deletion of a small piece of [[chromosome 22 (human)|chromosome 22]]. The deletion occurs near the middle of the [[chromosome]] at a location designated q11.2.
DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused by defects in the development of structures derived from the pharyngeal arches during embryogenesis.

It comprises of [[thymic hypoplasia]], [[hypocalcaemia,]] outflow tract defects of the heart, and dysmorphic facies.

==Historical Perspective==
DGS characteristics were first described in 1828 but adequately reported later in 1965 by Dr. Angelo DiGeorge, as a clinical trial that included immunodeficiency, hypoparathyroidism, and congenital heart disease.

Historically, DGS was grouped within a sphere of other syndromes such as Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS, collectively called '''22q11 deletion syndromes'''. They have the same genetic etiology but their varying phenotypes has has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.

==Classification==
There is no established system for the classification of DGS.

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

==Causes==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Differentiating [Disease] from Other Diseases==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.<br />
==Epidemiology and Demographics==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Risk Factors==
The only known risk factor is that of a family history of DGS.

==Screening==
Screening of DGS depends on known family history and then approaching with genetic studies in individual cases.

==Natural History, Complications, and Prognosis==
===Natural History ===
It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features.

===Complications===
Most patients with DGS may progress to develop severe recurrent infections, autoimmune diseases, and hematologic malignancies.

===Prognosis===
Prognosis is very poor, if left untreated, most patients die by 12 months of age.

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.

Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a [[cleft palate]] or other defect in the palate), [[autism]], other [[Learning disability|learning disabilities]], mild differences in facial features, and recurrent viral or fungal [[Infection|infections]] are common due to problems with the [[immune system]]'s T-cell mediated response.

===Physical Examination===

===Laboratory Findings===

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}
<references />

22q11.2 deletion syndrome overview

2020-08-17T13:13:56Z

Ayushijain: /* Natural History, Complications, and Prognosis */

<div style="-webkit-user-select: none;">
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
|-
| {{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==

'''22q11.2 deletion syndrome''' is a disorder caused by the deletion of a small piece of [[chromosome 22 (human)|chromosome 22]]. The deletion occurs near the middle of the [[chromosome]] at a location designated q11.2.
DiGeorge Syndrome (DGS) is a combination of signs and symptoms caused by defects in the development of structures derived from the pharyngeal arches during embryogenesis.

It comprises of [[thymic hypoplasia]], [[hypocalcaemia,]] outflow tract defects of the heart, and dysmorphic facies.

==Historical Perspective==
DGS characteristics were first described in 1828 but adequately reported later in 1965 by Dr. Angelo DiGeorge, as a clinical trial that included immunodeficiency, hypoparathyroidism, and congenital heart disease.

Historically, DGS was grouped within a sphere of other syndromes such as Shprintzen-Goldberg syndrome, velocardiofacial syndrome, Cayler cardiofacial syndrome, Sedlackova syndrome, conotruncal anomaly face syndrome, and DGS, collectively called '''22q11 deletion syndromes'''. They have the same genetic etiology but their varying phenotypes has has led to confusion in diagnosing patients with DGS, which causes potentially catastrophic delays in diagnosis.

==Classification==
There is no established system for the classification of DGS.

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

==Causes==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Differentiating [Disease] from Other Diseases==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.<br />
==Epidemiology and Demographics==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Risk Factors==
The only known risk factor is that of a family history of DGS.

==Screening==
Screening of DGS depends on known family history and then approaching with genetic studies in individual cases.

==Natural History, Complications, and Prognosis==
===Natural History ===
It is important to note that the broad spectrum of disease severity makes the evaluation of DGS particularly challenging. Cases involving significant cardiac, thymic, and craniofacial deficits are more easily recognizable than those lacking severe features.

===Complications===
Most patients with DGS may progress to develop severe recurrent infections, autoimmune diseases, and hematologic malignancies.

===Prognosis===
Prognosis is very poor, if left untreated, most patients die by 12 months of age.

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===

===Physical Examination===

===Laboratory Findings===

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}
<references />

22q11.2 deletion syndrome overview

2020-08-17T13:11:41Z

Ayushijain: /* Screening */

22q11.2 deletion syndrome overview

2020-08-12T20:26:09Z

Ayushijain: /* Differentiating [Disease] from Other Diseases */

22q11.2 deletion syndrome differential diagnosis

2020-08-12T20:25:01Z

Ayushijain: /* Differentiating DGS from other diseases on the basis of overlapping features */

22q11.2 deletion syndrome differential diagnosis

2020-08-12T20:24:10Z

Ayushijain: /* Differentiating DGS from other diseases on the basis of overlapping features: */

22q11.2 deletion syndrome differential diagnosis

2020-08-12T15:33:20Z

Ayushijain: /* Overview */

__NOTOC__
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/22q11.2_deletion_syndrome]]

{{CMG}}; {{AE}} : {{Ajane}}
==Overview==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation. All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section.

==Differentiating [Disease name] from other Diseases==
All of the clinical findings associated with 22q11.2 deletion syndrome (22q11.2DS) can also occur as an isolated anomaly in an otherwise healthy individual. Genetic disorders and teratogenic exposures that may cause a clinical phenotype similar to 22q11.2DS are discussed in this section. DGS must be differentiated from Smith-Lemli-Opitz syndrome, Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS), Alagille syndrome, VATER association, and CHARGE syndrome.

===Differentiating DGS from other diseases on the basis of overlapping features:===

<br />
{| class="wikitable"
|+
!Differential Diagnosis
!
!Physical Examination
!Lab findings.
!Clinical Manifestations
!
!
!
!
!
!+
!-
|-
|'''Single Gene Disorders'''
|
|
|
|
|
|
|
|
|
|
|
|-
|'''Disorder'''
|'''Gene Involved'''
|
|
|
|
|
|
|
|
|
|
|-
|Smith-Lemli-Opitz syndrome
|''DHCR7''
|
|
|Polydactyly
|Cleft Palate
|
|
|
|
|
|
|-
|Alagille syndrome
|''JAG1NOTCH2''
|
|
|Butterfly Vertebral
|Renal
|
|
|
|
|
|
|-
|CHARGE syndrome
|''CHD7''
|
|
|Congenital Heart disease
|Palatal Differences
|Atresia Choanae
|Coloboma
|Renal
|Growth Deficiency
|
|
|}
<br />

<br />
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;|Diseases
| colspan="6" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|'''Clinical manifestations'''
|-
| colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-

|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Smith-Lemli-Opitz syndrome
| style="background: #F5F5F5; padding: 5px;" |polydactyly<br />
| style="background: #F5F5F5; padding: 5px;" |cleft palate
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS)
| style="background: #F5F5F5; padding: 5px;" |Ear anomalies
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral defects
| style="background: #F5F5F5; padding: 5px;" |renal anomalies
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Alagille syndrome
| style="background: #F5F5F5; padding: 5px;" |Butterfly vertebrae.
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease
| style="background: #F5F5F5; padding: 5px;" |posterior embryotoxon
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |VATER association
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral
| style="background: #F5F5F5; padding: 5px;" |renal
| style="background: #F5F5F5; padding: 5px;" |limb
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |CHARGE syndrome
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease,
| style="background: #F5F5F5; padding: 5px;" |palatal differences,
| style="background: #F5F5F5; padding: 5px;" |atresia choanae,
| style="background: #F5F5F5; padding: 5px;" |coloboma,
| style="background: #F5F5F5; padding: 5px;" |renal,
| style="background: #F5F5F5; padding: 5px;" |growth deficiency,
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|}

==References==
{{Reflist|2}}

{{WH}}
{{WS}}
[[Category: (name of the system)]]

22q11.2 deletion syndrome differential diagnosis

2020-08-12T15:02:49Z

Ayushijain: /* Differentiating DGS from other diseases on the basis of overlapping features: */

__NOTOC__
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/22q11.2_deletion_syndrome]]

{{CMG}}; {{AE}} : {{Ajane}}
==Overview==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation.

==Differentiating [Disease name] from other Diseases==
DGS must be differentiated from Smith-Lemli-Opitz syndrome, Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS), Alagille syndrome, VATER association, and CHARGE syndrome.

===Differentiating DGS from other diseases on the basis of overlapping features:===

<br />
{| class="wikitable"
|+
!Differential Diagnosis
!History
!Physical Examination
!Lab findings.
!Clinical Manifestations
!
!
!
!
!
!+
!-
|-
|DiGeorges
|
|
|
|
|
|
|
|
|
|
|
|-
|Smith-Lemli-Opitz syndrome
|
|
|
|Polydactyly
|Cleft Palate
|
|
|
|
|
|
|-
|Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS)
|
|
|
|Ear anomalies
|Heart Disease
|Vertebral Defects
|Renal Anomalies
|
|
|
|
|-
|Alagille syndrome
|
|
|
|Butterfly Vertebral
|Renal
|
|
|
|
|
|
|-
|VATER association
|
|
|
|Heart Disease
|Vertebral
|Renal
|Limb
|
|
|
|
|-
|CHARGE syndrome
|
|
|
|Congenital Heart disease
|Palatal Differences
|Atresia Choanae
|Coloboma
|Renal
|Growth Deficiency
|
|
|}
<br />

<br />
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;|Diseases
| colspan="6" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|'''Clinical manifestations'''
|-
| colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-

|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Smith-Lemli-Opitz syndrome
| style="background: #F5F5F5; padding: 5px;" |polydactyly<br />
| style="background: #F5F5F5; padding: 5px;" |cleft palate
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS)
| style="background: #F5F5F5; padding: 5px;" |Ear anomalies
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral defects
| style="background: #F5F5F5; padding: 5px;" |renal anomalies
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Alagille syndrome
| style="background: #F5F5F5; padding: 5px;" |Butterfly vertebrae.
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease
| style="background: #F5F5F5; padding: 5px;" |posterior embryotoxon
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |VATER association
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral
| style="background: #F5F5F5; padding: 5px;" |renal
| style="background: #F5F5F5; padding: 5px;" |limb
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |CHARGE syndrome
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease,
| style="background: #F5F5F5; padding: 5px;" |palatal differences,
| style="background: #F5F5F5; padding: 5px;" |atresia choanae,
| style="background: #F5F5F5; padding: 5px;" |coloboma,
| style="background: #F5F5F5; padding: 5px;" |renal,
| style="background: #F5F5F5; padding: 5px;" |growth deficiency,
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|}

==References==
{{Reflist|2}}

{{WH}}
{{WS}}
[[Category: (name of the system)]]

22q11.2 deletion syndrome epidemiology and demographics

2020-08-12T14:54:09Z

Ayushijain: /* Overview */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.<ref name=":0">McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. ''Nat Rev Dis Primers''. 2015;1:15071. Published 2015 Nov 19. doi:10.1038/nrdp.2015.71</ref>

==Epidemiology and Demographics==
===Incidence and Prevalence===
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births . The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000. <ref name=":0" /> There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produce embryonically lethal phenotypes, which was observable in animal studies.

The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does not undergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations..

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome epidemiology and demographics

2020-08-12T14:53:19Z

Ayushijain: /* Incidence and Prevalence */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.

==Epidemiology and Demographics==
===Incidence and Prevalence===
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births . The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.<ref name=":0" /> There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produce embryonically lethal phenotypes, which was observable in animal studies.

The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does not undergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations..

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome epidemiology and demographics

2020-08-12T14:52:02Z

Ayushijain: /* Overview */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.<ref>McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. ''Nat Rev Dis Primers''. 2015;1:15071. Published 2015 Nov 19. doi:10.1038/nrdp.2015.71</ref>

==Epidemiology and Demographics==
===Incidence and Prevalence===
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births . The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000...There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produce embryonically lethal phenotypes, which was observable in animal studies.

The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does not undergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations..

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome overview

2020-08-12T14:51:36Z

Ayushijain: /* Overview */

22q11.2 deletion syndrome epidemiology and demographics

2020-08-12T14:49:24Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{Ajane}}

==Overview==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.<ref name=":0" />

==Epidemiology and Demographics==
===Incidence and Prevalence===
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births . The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000...There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produce embryonically lethal phenotypes, which was observable in animal studies.

The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does not undergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations..

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome epidemiology and demographics

2020-08-12T14:48:39Z

Ayushijain: /* Overview */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births. Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000.<ref name=":0" />

==Epidemiology and Demographics==
===Incidence and Prevalence===
22q11.2 deletion syndrome affects an estimated 25 in 100,000 live births . The condition may be more common, however, because some people with the deletion have few signs and symptoms and may not have been diagnosed.
Microdeletion of 22q11.2 is the most common microdeletion syndrome, affecting approximately 0.1% of fetuses.. The rate of 22q11.2 microdeletion in live births occurs at an estimated rate of 1 in 4000 to 6000...There are several explanations for the variance in fetal versus live birth prevalence. Firstly, current evidence may not comprise a large enough population. Secondly, 22q11.2 microdeletions may produce embryonically lethal phenotypes, which was observable in animal studies.

The prevalence of 22q11.2 microdeletion may be more common than supported in literature due to several factors. Firstly, not every patient with this microdeletion presents with several craniofacial abnormalities and hence does not undergo genetic testing. African-American children, for example, may not have the craniofacial abnormalities characteristic of DGS in other races. Secondly, access to healthcare, specifically genetic testing, is not available to every individual that might have the microdeletion, regardless of the severity of craniofacial dysmorphism. Further population studies are therefore needed to fully understand the extent and spectrum of 22q11.2 microdeletions in different populations..

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]
<references />

22q11.2 deletion syndrome pathophysiology

2020-08-12T14:44:30Z

Ayushijain: /* Pathophysiology */

<div style="-webkit-user-select: none;">
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
|-
| {{#ev:youtube|https://https://www.youtube.com/watch?v=YdDs92gaWl8|350}}
|-
|}
__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==

==Pathophysiology==
The main factor leading to DGS is the deletion of 22q11.2, which encodes over 90 genes. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. These included the '''velo-cardio-facial syndrome''' (also called '''Shprintzen's syndrome'''), '''DiGeorge syndrome''', '''hearing loss with craniofacial syndromes''' and '''conotruncal anomaly face syndrome''', thymic hypoplasia, cleft palate, psychiatric disorders, and hypocalcaemia. The acronym '''CATCH-22''' ('''C''' = cardiac defects, '''A''' = abnormal facies, '''T''' = thymic hypoplasia, '''C''' = cleft palate, '''H''' = hypocalcemia from parathyroid aplasia, '''22''' = microdeletions in chromosome 22) is sometimes used, although it is widely rejected because of the negative connotations with [[Catch-22 (logic)|Catch-22]] meaning a 'no-win' situation.

In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

The syndrome is caused by genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.

DiGeorge syndrome causes migration defects of [[neural crest]]-derived tissues, particularly affecting development of the third and fourth [[Branchial pouches]] (pharyngeal pouches). Also affected is the thymus gland; a mediastinal organ largely responsible for differentiation and induction of tolerance in T-cells. Impaired immune function results principally from this etiology.

===Genetics===
[[Image:Autodominant.jpg|thumb|left|22q11.2 deletion syndrome is inherited in an [[autosomal dominant]] pattern.]]
Most people with 22q11.2 deletion syndrome are missing about 3 million [[base pair]]s (the building blocks of DNA) on one copy of [[chromosome 22 (human)|chromosome 22]] in each cell. This region contains about 30 genes, but many of these genes have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes.

Researchers have not yet identified all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of one particular gene on chromosome 22, ''[[TBX1]]'', is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). A loss of this gene does not appear to cause learning disabilities, however. Additional genes in the deleted region are likely to contribute to the signs and symptoms of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome can be inherited in an [[autosomal dominant]] manner. Almost all (about 93%) of cases have a de novo (new to the family) deletion of 22q11.2 but about 7% inherit the 22q11.2 deletion from a parent. Children of an individual with deletion 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. [[Prenatal testing]], such as [[amniocentesis]], is available for pregnancies determined to be at risk. Also pregnancies who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination may be offered prenatal testing. [[Genetic counseling]] may be helpful for families who may have DiGeorge syndrome. Because most of the signs of this cluster of defects can also be inherited as [[autosomal recessive]] or [[x-linked]] traits, only genetic testing of both parents can determine with any certainty the likelihood these anomalies occurring in any subsequent children.

===Associated Disorders===
* [[Congenital heart disease]] (74% of individuals), particularly conotruncal malformations ([[tetralogy of Fallot]], [[interrupted aortic arch]], [[ventricular septal defect]], and [[persistent truncus arteriosus]])
* [[Immune deficiency]]
* [[Renal]] anomalies (37%)
* [[Autoimmune disorders]]
* [[Autism]] and [[Autism spectrum disorders]]

[[Thymus]], [[parathyroid gland]]s and [[heart]] derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to [[yeast infections]].
[[Category:Hematology]]
==References==
{{Reflist|2}}

{{WH}}
{{WS}}

]

22q11.2 deletion syndrome classification

2020-08-04T17:52:05Z

Ayushijain: /* Classification */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Based on the subtype, DGS may be classified as either partial or complete.

==Classification==

There is no established system for the classification of DGS.

However, based on the severity, it may be classified as partial DGS and complete DGS.

Since symptoms of DiGeorge syndrome were variable and the underlying cause (deletions of 22q11.2) is responsible for other related/overlapping syndromes, using terms such as 'complete' and 'partial' DiGeorge syndrome is in reference to individual cases which had all the characteristic signs and symptoms (e.g., hypoparathyroidism, absent thymus, and heart disease) versus those with only some of them.<ref>Akar NA, Adekile AD. Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias, macrothrombocytopenia and platelet dysfunction. Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2007 ;16(4):318-320. DOI: 10.1159/000102157.</ref>

==References==
{{Reflist|2}}
{{WH}}
{{WS}}
[[Category: (name of the system)]]

22q11.2 deletion syndrome causes

2020-07-11T01:24:16Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Causes==
Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS.[1] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the [[behavioral and developmental abnormalities]] seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome causes

2020-07-11T01:22:32Z

Ayushijain: /* Causes */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Most cases are linked to microdeletion of chromosome 22, at the long arm (q) at the 11.2 locus.

==Causes==
Approximately 90% of DGS cases are due to deletion in chromosome 22, more specifically on the long arm (q) at the 11.2 locus (22q11.2). Most of these mutations arise de novo with no genetic abnormalities noted in the genome of the parents of children with DGS.[1] Researchers have identified over 90 different genes at this locus, some of which they have studied in mouse models. T-box transcription factor 1 (TBX1) is the most studied gene , which correlates with severity of DGS such as defects in the development of the heart, thymus, and parathyroid glands of mouse models. TBX1 also correlates with neuromicrovascular anomalies, which may be responsible for the behavioral and developmental abnormalities seen in DGS.<ref>Cioffi S, Martucciello S, Fulcoli FG, Bilio M, Ferrentino R, Nusco E, Illingworth E. Tbx1 regulates brain vascularization. Hum. Mol. Genet. 2014 Jan 01;23(1):78-89. </ref><ref>Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH, Oghalai J, Curran S, Murphy KC, Monks S, Williams N, O'Donovan MC, Owen MJ, Scambler PJ, Lindsay E. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc. Natl. Acad. Sci. U.S.A. 2006 May 16;103(20):7729-34.</ref>

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WS}}
{{WH}}

22q11.2 deletion syndrome differential diagnosis

2020-07-11T00:41:32Z

Ayushijain:

__NOTOC__
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/22q11.2_deletion_syndrome]]

{{CMG}}; {{AE}} : {{Ajane}}
==Overview==
DGS must be differentiated from other diseases that cause similar clinical features and have a broad spectrum of presentation.

==Differentiating [Disease name] from other Diseases==
DGS must be differentiated from Smith-Lemli-Opitz syndrome, Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS), Alagille syndrome, VATER association and CHARGE syndrome.

===Differentiating DGS from other diseases on the basis of overlapping features:===

<br />
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;|Diseases
| colspan="6" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|'''Clinical manifestations'''
|-
| colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-

|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;|
! style="background: #4479BA; color: #FFFFFF; text-align: center;|
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Smith-Lemli-Opitz syndrome
| style="background: #F5F5F5; padding: 5px;" |polydactyly<br />
| style="background: #F5F5F5; padding: 5px;" |cleft palate
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Oculo-auriculo vertebral (Goldenhar) syndrome (OAVS)
| style="background: #F5F5F5; padding: 5px;" |Ear anomalies
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral defects
| style="background: #F5F5F5; padding: 5px;" |renal anomalies
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Alagille syndrome
| style="background: #F5F5F5; padding: 5px;" |Butterfly vertebrae.
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease
| style="background: #F5F5F5; padding: 5px;" |posterior embryotoxon
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |VATER association
| style="background: #F5F5F5; padding: 5px;" |heart disease
| style="background: #F5F5F5; padding: 5px;" |vertebral
| style="background: #F5F5F5; padding: 5px;" |renal
| style="background: #F5F5F5; padding: 5px;" |limb
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |CHARGE syndrome
| style="background: #F5F5F5; padding: 5px;" |congenital heart disease,
| style="background: #F5F5F5; padding: 5px;" |palatal differences,
| style="background: #F5F5F5; padding: 5px;" |atresia choanae,
| style="background: #F5F5F5; padding: 5px;" |coloboma,
| style="background: #F5F5F5; padding: 5px;" |renal,
| style="background: #F5F5F5; padding: 5px;" |growth deficiency,
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|}

==References==
{{Reflist|2}}

{{WH}}
{{WS}}
[[Category: (name of the system)]]

22q11.2 deletion syndrome classification

2020-07-11T00:26:30Z

Ayushijain: /* Classification */

__NOTOC__
{{22q11.2 deletion syndrome}}
{{CMG}} {{AE}} {{ajane}}

==Overview==
Based on the subtype, DGS may be classified as either partial or complete.

==Classification==

There is no established system for the classification of DGS.

However, based on the severity, it may be classified as partial DGS and complete DGS.

Since symptoms of DiGeorge syndrome were variable and the underlying cause (deletions of 22q11.2) is responsible for other related/overlapping syndromes, using terms such as 'complete' and 'partial' DiGeorge syndrome is in reference to individual cases which had all the characteristic signs and symptoms (e.g., hypoparathyroidism, absent thymus, and heart disease) versus those with only some of them.<ref>Hernández-Nieto L, Yamazaki-Nakashimada MA, Lieberman-Hernández E, Espinosa-Padilla SE. Autoimmune thrombocytopenic purpura in partial DiGeorge syndrome: case presentation. ''J Pediatr Hematol Oncol''. August 2011; 33(6):465-466.</ref>

==References==
{{Reflist|2}}
{{WH}}
{{WS}}
[[Category: (name of the system)]]

File:Cv pic2.jpg

2020-07-10T21:07:33Z

Ayushijain:

22q11.2 deletion syndrome overview

2020-07-10T19:33:00Z

Ayushijain: overview

22q11.2 deletion syndrome overview

2020-07-10T19:30:59Z

Ayushijain:

22q11.2 deletion syndrome physical examination

2020-07-10T19:13:52Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==
History and physical are vital in the diagnosis and assessment of DGS. Most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

==Physical Examination==
===Head===
* [[Palatal]] abnormalities (69%), particularly [[velopharyngeal incompetence]] (VPI), submucosal [[cleft palate]], and [[cleft palate]]; characteristic facial features (present in the majority of Caucasian individuals) including [[hypertelorism]].

===Ear===
* [[Hearing impairment|Hearing loss]] (both [[conductive]] and [[sensorineural]]) ([[Hearing loss with craniofacial syndromes]])

===Throat===
* Laryngotracheoesophageal anomalies

===Extremities===
* [[Skeletal]] [[abnormalities]]

===Neurologic===
* [[Autism]] and [[Autism spectrum disorders]]
* [[Seizures]] (without [[hypocalcemia]])
* [[Learning difficulties]] (70-90%)

A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent with aortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.

Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia

Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.

Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.<ref>Lackey AE, Muzio MR. DiGeorge Syndrome. [Updated 2020 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK549798/</nowiki></ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome physical examination

2020-07-10T19:13:13Z

Ayushijain: /* Physical Examination */

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}

==Overview==
History and physical are vital in the diagnosis and assessment of DGS. Most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

==Physical Examination==
===Head===
* [[Palatal]] abnormalities (69%), particularly [[velopharyngeal incompetence]] (VPI), submucosal [[cleft palate]], and [[cleft palate]]; characteristic facial features (present in the majority of Caucasian individuals) including [[hypertelorism]].

===Ear===
* [[Hearing impairment|Hearing loss]] (both [[conductive]] and [[sensorineural]]) ([[Hearing loss with craniofacial syndromes]])

===Throat===
* Laryngotracheoesophageal anomalies

===Extremities===
* [[Skeletal]] [[abnormalities]]

===Neurologic===
* [[Autism]] and [[Autism spectrum disorders]]
* [[Seizures]] (without [[hypocalcemia]])
* [[Learning difficulties]] (70-90%)

A complete cardiopulmonary evaluation can reveal murmurs, cyanosis, clubbing, or edema consistent with aortic arch anomalies, conotruncal defects (e.g., tetralogy of Fallot, truncus arteriosus, pulmonary atresia with ventricular septal defect, transposition of the great vessels, interrupted aortic arch), or tricuspid atresia.

Recurrent sinopulmonary infections due to T cell deficiency as a result of thymic hypoplasia

Signs of hypocalcemia, including twitching and muscle spasm, may be evident as a result of parathyroid hypoplasia. Chvostek's and Trousseau's signs may be positive.

Delayed development, unusual behavior, or signs of psychiatric disorders may be observable.<ref>Lackey AE, Muzio MR. DiGeorge Syndrome. [Updated 2020 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK549798/</nowiki></ref>

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Hematology]]

22q11.2 deletion syndrome history and symptoms

2020-07-10T19:07:14Z

Ayushijain:

__NOTOC__
{{22q11.2 deletion syndrome}}

{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{ajane}}

==Overview==
A detailed history and physical is vital in the diagnosis and assessment of DiGeorge syndrome.

==History==
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.

Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.<ref>McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011 Jan;90(1):1-18.</ref>

These findings can be associated with delayed speech development and learning disabilities. Later in life, abnormal behavior in the setting of poor developmental history may be the chief presenting symptom of DGS.<ref>McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071. </ref>

A detailed history may reveal the following:

* Family history of diagnosed or suspected DGS
* Abnormal genetic testing results of family members
* Delays in the achievement of developmental milestones
* Behavioral disturbance
* Cyanosis, exercise intolerance, or symptoms
* Recurrent infections secondary to T-cell deficiency
* Speech difficulty
* Difficulty feeding and/or failure to thrive
* Muscle spasms, twitching, tetany, seizure

==Symptoms==
Individuals with a 22q11 deletion can suffer from a range of over 200 possible symptoms, ranging from the mild to the very serious. Possible symptoms are:
* An [[immune deficiency]] regardless of their clinical presentation (77%) - recurrent infections
* Significant feeding problems (30%)
* [[Learning difficulties]] (70-90%)
* [[Hearing impairment|Hearing loss]]
* [[Seizures]]

===Presentation===
The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a [[cleft palate]] or other defect in the palate), [[autism]], other [[learning disability|learning disabilities]], mild differences in facial features, and recurrent viral or fungal [[infection]]s are common due to problems with the [[immune system]]'s T-cell mediated response. DiGeorge syndrome is often first spotted when the affected newborn begins convulsing from hypocalcemia due to an absence of parathyroid and parathyroid hormone. Affected individuals may also have kidney abnormalities, significant feeding difficulties, [[autoimmune disorder]]s such as [[rheumatoid arthritis]], and an increased risk of developing mental illnesses.<ref name="Bebbane_2006_psychosis">{{cite journal |author=Debbané M, Glaser B, David MK, Feinstein C, Eliez S |title=Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications |journal=Schizophr. Res. |volume=84 |issue=2-3 |pages=187-93 |year=2006 |pmid=16545541 |doi=10.1016/j.schres.2006.01.019}}</ref>

Microdeletions in chromosomal region 22q11 are associated with a roughly 30-fold increased risk of [[schizophrenia]]<ref name="Horowitz_2005_SCHZ">{{cite journal |author=Bassett AS, Chow EW, AbdelMalik P, Gheorghiu M, Husted J, Weksberg R |title=The schizophrenia phenotype in 22q11 deletion syndrome |journal=Am J Psychiatry |volume=160 |issue=9 |pages=1580-6 |year=2003 |pmid=12944331 |doi=}}</ref> and are frequently detected in schizophrenic patients. Different studies provide different occurrence rates, ranging from 0.5 to 3%, compared with the overall 0.025% risk of the 22q11 deletion syndrome in the general population.<ref name="Horowitz_2005_survey_SCHZ">{{cite journal |author=Horowitz A, Shifman S, Rivlin N, Pisanté A, Darvasi A |title=A survey of the 22q11 microdeletion in a large cohort of schizophrenia patients |journal=Schizophr. Res. |volume=73 |issue=2-3 |pages=263-7 |year=2005 |pmid=15653270 |doi=10.1016/j.schres.2004.02.008}}</ref>

===Cognitive and language problems===
====Cognitive deficits====
Children with 22q11.2 have a specific profile in neuropsychological tests. They usually have a low IQ (50-80) but with better verbal than procedural functions. Especially big problems are usually within arithmetic and executive skills. Familial transmission of the disease seems to result in worse cognitive impairments than the de novo cases. It has been speculated that the observed cognitive problems arise from visuo-spatial problems.

Noteworthy is that these patients are a specifically high-risk group for developing schizophrenia. 30% have at least one incident of [[psychosis]] and about a quarter develop actual [[schizophrenia]].<ref>{{cite journal |author=Zinkstok J, van Amelsvoort T |title=Neuropsychological profile and neuroimaging in patients with 22Q11.2 Deletion Syndrome: a review |journal=Child Neuropsychol |volume=11 |issue=1 |pages=21-37 |year=2005 |pmid=15823981 |doi=10.1080/09297040590911194}}</ref>

====Speech and Language====
Current research demonstrates there is a unique profile of speech and language impairments associated with 22q11.2 deletion syndrome. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. Common problems include hypernasality, language delays, and speech sound errors.<ref name="Dantonio">{{cite journal |author=D'Antonio LL, Scherer NJ, Miller LL, Kalbfleisch JH, Bartley JA |title=Analysis of speech characteristics in children with velocardiofacial syndrome (VCFS) and children with phenotypic overlap without VCFS |journal=Cleft Palate Craniofac. J. |volume=38 |issue=5 |pages=455-67 |year=2001 |pmid=11522167}}</ref><ref name="Scherer1999">{{cite journal |author=Scherer NJ, D'Antonio LL, Kalbfleisch JH |title=Early speech and language development in children with velocardiofacial syndrome |journal=Am. J. Med. Genet. |volume=88 |issue=6 |pages=714-23 |year=1999 |pmid=10581495}}</ref><ref name="Scherer2001">{{cite journal |author=Scherer NJ, D'Antonio LL, Rodgers JR |title=Profiles of communication disorder in children with velocardiofacial syndrome: comparison to children with Down syndrome |journal=Genet. Med. |volume=3 |issue=1 |pages=72-8 |year=2001 |pmid=11339384 |doi=}}</ref>

Hypernasality occurs when air escapes through the nose during the production of oral speech sounds resulting in reduced [[intelligibility]]. This is a common characteristic in the speech and language profile because 69% of children have [[palatal]] abnormalities. If the structure of the soft palate [[Soft palate|velum]] is such that it does not stop the flow of air from going up to the [[nasal cavity]], it will cause hypernasal speech. This phenomenon is referred as [[velopharyngeal inadequacy]] VPI. Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery. <ref name="Dantonio"> </ref>
<ref name="Eliez">{{cite journal |author=Eliez S, Palacio-Espasa F, Spira A, ''et al'' |title=Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and language phenotypes |journal=Eur Child Adolesc Psychiatry |volume=9 |issue=2 |pages=109-14 |year=2000 |pmid=10926060 |doi=}}</ref><ref name="Robin">{{cite journal |author=Robin NH, Shprintzen RJ |title=Defining the clinical spectrum of deletion 22q11.2 |journal=J. Pediatr. |volume=147 |issue=1 |pages=90-6 |year=2005 |pmid=16027702 |doi=10.1016/j.jpeds.2005.03.007}}</ref><ref name="Scherer1999"> </ref><ref name="Solot">{{cite journal |author=Solot CB, Knightly C, Handler SD, ''et al'' |title=Communication disorders in the 22Q11.2 microdeletion syndrome |journal=J Commun Disord |volume=33 |issue=3 |pages=187-203; quiz 203-4 |year=2000 |pmid=10907715 |doi=10.1016/S0021-9924(00)00018-6}}</ref>

Difficulties acquiring vocabulary and formulating spoken language (expressive language deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion. Vocabulary acquisition is often severely delayed for preschool age children. In some recent studies, children had a severely limited vocabulary or were still nonverbal at 2-3 years of age. School age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences. Receptive language, which is the ability to comprehend, retain, or process spoken language, can also be impaired although not usually with the same severity as expressive language impairments.
<ref name="Persson">{{cite journal |author=Persson C, Niklasson L, Oskarsdóttir S, Johansson S, Jönsson R, Söderpalm E |title=Language skills in 5-8-year-old children with 22q11 deletion syndrome |journal=Int J Lang Commun Disord |volume=41 |issue=3 |pages=313-33 |year=2006 |pmid=16702096 |doi=10.1080/13682820500361497}}</ref><ref name="Robin"> </ref><ref name="Scherer1999"> </ref><ref name="Solot"> </ref>

[[Articulation]] errors are commonly present in children with 22q11.2 deletion syndrome. These errors include a limited phonemic (speech sound) inventory and the use of compensatory articulation strategies resulting in reduced intelligibility. The phonemic inventory typically produced consists of sounds made in the front or back of the vocal tract such as: /p/, /w/, /j/, /m/, /n/, and glottal stops. Mid vocal tract sounds are completely absent. Compensatory articulation errors made by this population of children include: [[glottal stop]]s, nasal substitutions, pharyngeal fricatives, linguapalatal sibilants, reduced pressure on consonant sounds, or a combination of these symptoms. Of these errors, glottal stops have the highest frequency of occurrence. It is reasoned that a limited phonemic inventory and the use of compensatory articulation strategies is present due to the structural abnormalities of the palate. The speech impairments exhibited by this population are more severe during the younger ages and show a trend of gradual improvement as the child matures. <ref name="Dantonio"> </ref><ref name="Robin"> </ref>

==References==
{{Reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}