Gardner's syndrome: Difference between revisions
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New genetic and molecular information has caused some genetic disorders to be split into multiple entities while other genetic disorders merge into one condition. After existing for most of the second half of the 20th century, Gardner's syndrome has vanished as a separate entity. It has been merged into [[familial adenomatous polyposis]] (FAP) and is now considered simply a [[phenotypic]] variant of FAP. | New genetic and molecular information has caused some genetic disorders to be split into multiple entities while other genetic disorders merge into one condition. After existing for most of the second half of the 20th century, Gardner's syndrome has vanished as a separate entity. It has been merged into [[familial adenomatous polyposis]] (FAP) and is now considered simply a [[phenotypic]] variant of FAP. | ||
==DIfferentiating Gardner's syndrome from other diseases== | |||
<small> | |||
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center" | |||
|+ | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disease}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gene}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Chromosome}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differentiating Features}} | |||
! colspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Components of MEN}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}} | |||
|- | |||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Parathyroid}} | |||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pitutary}} | |||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pancreas}} | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[von Hippel-Lindau syndrome]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Von Hippel–Lindau tumor suppressor | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |3p25.3 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Angiomatosis, | |||
* Hemangioblastomas, | |||
* Pheochromocytoma, | |||
* Renal cell carcinoma, | |||
* Pancreatic cysts (pancreatic serous cystadenoma) | |||
* Endolymphatic sac tumor, | |||
* Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | + | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
* In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Carney complex]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| PRKAR1A | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| 17q23-q24 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| | |||
* Myxomas of the heart | |||
* Hyperpigmentation of the skin (lentiginosis) | |||
* Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Neurofibromatosis type 1]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|RAS | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|17 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| | |||
* [[Scoliosis]] | |||
* Learning disabilities | |||
* [[Vision]] disorders | |||
* Cutaneous [[lesion]]s | |||
* [[Epilepsy]]. | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |'''<u>Prenatal</u>''' | |||
* Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus. | |||
'''<u>Postnatal</u>''' | |||
Cardinal Clinical Features" are required for positive diagnosis. | |||
* Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. | |||
* Two or more neurofibromas of any type or 1 plexiform neurofibroma | |||
* Freckling in the axillary (Crowe sign) or inguinal regions | |||
* Optic glioma | |||
* Two or more Lisch nodules (pigmented iris hamartomas) | |||
* A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Li-Fraumeni syndrome]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |TP53 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Early onset of diverse amount of [[cancer]]s such as | |||
* [[Sarcoma]] | |||
* [[Cancer]]s of | |||
** [[Breast]] | |||
** [[Brain]] | |||
** [[Adrenal gland]]s | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
'''<u>Criteria</u>''' | |||
* Sarcoma at a young age (below 45) | |||
* A first-degree relative diagnosed with any cancer at a young age (below 45) | |||
* A first or second degree relative with any cancer diagnosed before age 60. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Gardner's syndrome]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | APC | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 5q21 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Multiple polyps in the colon | |||
* Osteomas of the skull | |||
* Thyroid cancer, | |||
* Epidermoid cysts, | |||
* Fibromas | |||
* Desmoid tumors | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
* Colonoscopy | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Multiple endocrine neoplasia type 2]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |''RET'' | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Medullary thyroid carcinoma]] (MTC) | |||
* [[Pheochromocytoma]] | |||
* Primary [[hyperparathyroidism]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | + | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Hypercalcemia]] | |||
* [[Hypophosphatemia]], | |||
* Elevated [[parathyroid hormone]], | |||
* Elevated [[norepinephrine]] | |||
'''<u>Criteria</u>''' | |||
Two or more specific endocrine tumors | |||
* [[Medullary thyroid carcinoma]] | |||
* [[Pheochromocytoma]] | |||
* [[Parathyroid]] hyperplasia | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Cowden syndrome]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |PTEN | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Hamartomas | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* ''PTEN'' mutation probability risk calculator | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Acromegaly]]/[[gigantism]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Enlargement of the [[hand]]s, [[feet]], [[nose]], [[lip]]s and [[ear]]s, and a general thickening of the [[skin]] | |||
* [[Hypertrichosis]] | |||
* [[Hyperpigmentation]] | |||
* [[Hyperhidrosis]] | |||
* [[Carpal tunnel syndrome]]. | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* An elevated concentration of serum [[Growth hormone|growth hormone (GH)]] and [[Insulin-like growth factor|insulin-like growth factor 1(IGF-1)]] levels is diagnostic of acromegaly. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pituitary adenoma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Visual field defect]]s classically [[bitemporal hemianopsia]] | |||
* Increased [[intracranial pressure]] | |||
* [[Migraine]] | |||
* [[Lateral rectus]] palsy | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
:*Elevated serum level of [[prolactin]] | |||
:*Elevated or decreased serum level of [[adrenocorticotropic hormone]] (ACTH) | |||
:*Elevated or decreased serum level of [[growth hormone]] (GH) | |||
:*Elevated or decreased serum level of [[thyroid-stimulating hormone]] (TSH) | |||
:*Elevated or decreased serum level of [[follicle-stimulating hormone]] (FSH) | |||
:*Elevated or decreased serum level of [[luteinizing hormone]] (LH) | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hyperparathyroidism]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
* [[Kidney stone]]s | |||
* [[Hypercalcemia]], | |||
* [[Constipation]] | |||
* [[Peptic ulcer]]s | |||
* [[Depression]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level is diagnostic of primary hyperparathyroidism. | |||
* Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum [[parathyroid hormone]] level and low to normal serum [[calcium]]. | |||
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level in post [[Kidney transplantation|renal transplant]] patients is diagnostic of tertiary hyperparathyoidism. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pheochromocytoma]]/[[paraganglioma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
''VHL'' | |||
''RET'' | |||
''NF1'' | |||
''SDHB'' | |||
''SDHD'' | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Characterized by | |||
* Episodic [[hypertension]] | |||
* [[Palpitation]]s | |||
* [[Anxiety]] | |||
* [[Diaphoresis]] | |||
* [[Weight loss]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Adrenocortical carcinoma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
*p53 | |||
*Retinoblastoma h19 | |||
*Insulin-like growth factor II (IGF-II) | |||
*p57<sup>kip2</sup> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17p, 13q | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Cushing syndrome]] ([[cortisol]] hypersecretion) | |||
* [[Conn syndrome]] ([[aldosterone]] hypersecretion) | |||
* [[virilization]] ([[testosterone]] hypersecretion) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Increased serum glucose | |||
* Increased urine cortisol | |||
* Serum androstenedione and dehydroepiandrosterone | |||
* Low serum potassium | |||
* Low plasma renin activity | |||
* High serum aldosterone. | |||
* Excess serum estrogen. | |||
|- | |||
| colspan="8" style="padding: 5px 5px; background: #F5F5F5;" |<small>Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013<ref name="pmid23917672">{{cite journal| author=Toledo SP, Lourenço DM, Toledo RA| title=A differential diagnosis of inherited endocrine tumors and their tumor counterparts. | journal=Clinics (Sao Paulo) | year= 2013 | volume= 68 | issue= 7 | pages= 1039-56 | pmid=23917672 | doi=10.6061/clinics/2013(07)24 | pmc=PMC3715026 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23917672 }} </ref> </small> | |||
|} | |||
</small> | |||
==References== | ==References== |
Latest revision as of 19:05, 18 October 2017
Gardner's syndrome | |
OMIM | 175100 |
---|---|
DiseasesDB | 5094 |
MedlinePlus | 000266 |
eMedicine | med/2712 derm/163 |
MeSH | D005736 |
Gardner's syndrome is a genetic disorder characterized by the presence of multiple polyps in the colon together with tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The countless polyps in the colon predispose to the development of colon cancer.
Inheritance
Gardner's syndrome is inherited in an autosomal dominant manner. Typically, one parent has Gardner's syndrome. Each of their children, male and female alike, are at 50% risk of inheriting the gene for Gardner's syndrome and manifesting it.
Diagnosis
Gardner's syndrome can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas which give a "cotton-wool" appearance to the jaws, as well as multiple odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), in addition to multiple adenomatous polyps of the colon.
Eponym
The syndrome is named for Eldon J. Gardner (1909-1989), a college teacher of genetics, who first described it in 1951.[1] Gardner had been introduced to a large Utah family with the syndrome by a premedical student in his course in genetics.
Genetics
Gardner's syndrome is now known to be caused by mutation in the APC gene located in chromosome 5q21 (band q21 on chromosome 5). This is the same gene as is mutant in familial adenomatous polyposis (FAP), a more common disease that also predisposes to colon cancer.
New genetic and molecular information has caused some genetic disorders to be split into multiple entities while other genetic disorders merge into one condition. After existing for most of the second half of the 20th century, Gardner's syndrome has vanished as a separate entity. It has been merged into familial adenomatous polyposis (FAP) and is now considered simply a phenotypic variant of FAP.
DIfferentiating Gardner's syndrome from other diseases
Disease | Gene | Chromosome | Differentiating Features | Components of MEN | Diagnosis | ||
---|---|---|---|---|---|---|---|
Parathyroid | Pitutary | Pancreas | |||||
von Hippel-Lindau syndrome | Von Hippel–Lindau tumor suppressor | 3p25.3 |
|
- | - | + |
|
Carney complex | PRKAR1A | 17q23-q24 |
|
- | - | - |
|
Neurofibromatosis type 1 | RAS | 17 | - | - | - | Prenatal
Postnatal Cardinal Clinical Features" are required for positive diagnosis.
| |
Li-Fraumeni syndrome | TP53 | 17 | Early onset of diverse amount of cancers such as | - | - | - |
Criteria
|
Gardner's syndrome | APC | 5q21 |
|
- | - | - |
|
Multiple endocrine neoplasia type 2 | RET | - |
|
+ | - | - |
Criteria Two or more specific endocrine tumors
|
Cowden syndrome | PTEN | - | Hamartomas | - | - | - |
|
Acromegaly/gigantism | - | - |
|
- | + | - |
|
Pituitary adenoma | - | - |
|
- | + | - |
|
Hyperparathyroidism | - | - | - | + | - | - |
|
Pheochromocytoma/paraganglioma |
VHL RET NF1 SDHB SDHD |
- | Characterized by | - | - | - |
|
Adrenocortical carcinoma |
|
17p, 13q |
|
- | - | - |
|
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013[2] |
References
- ↑ Gardner EJ (1951). "A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum". Am J Hum Genet. 3: 167–76. PMC 1716321. PMID 14902760.
- ↑ Toledo SP, Lourenço DM, Toledo RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.
External Links
Template:Digestive system neoplasia