Williams syndrome: Difference between revisions

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{{SK}} Beuren-Williams syndrome; supravalvular aortic stenosis hypercalcemia syndrome; Williams syndrome; Williams-Beuren syndrome; Chromosome 7q11.23 deletion syndrome, 1.5- to 1.8-mb; WMS;  WS
{{SK}} [[Beuren-Williams syndrome]]; [[supravalvular aortic stenosis hypercalcemia syndrome]]; [[Williams syndrome]]; Williams-Beuren syndrome; [[Chromosome 7q11.23 deletion syndrome,]] 1.5- to 1.8-mb; WMS;  WS
==Overview==
==Overview==
'''Williams syndrome''' (also '''Williams-Beuren syndrome''') is a rare [[genetic disorder]] characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers, coupled with unpredictably occurring negative outbursts; [[mental retardation]] coupled with unusual (for persons who are diagnosed as mentally retarded)  [[language]] skills; a love for music; and cardiovascular problems, such as [[supravalvular aortic stenosis]] and transient [[hypercalcaemia]].
'''Williams syndrome''' (also ''' Williams-Beuren syndrome''') is a rare [[genetic disorder]] characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers, coupled with unpredictably occurring negative outbursts; [[mental retardation]] coupled with unusual (for persons who are diagnosed as mentally retarded)  [[language]] skills; a love for music; and [[cardiovascular]] problems, such as [[supravalvular aortic stenosis]] and transient [[hypercalcemia]].


==Historical Perspective==
==Historical Perspective==
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==Pathophysiology==
==Pathophysiology==
It is thought that Williams syndrome is caused by deletion of genetic material from the region q11.2 of chromosome 7.  
It is thought that [[Williams syndrome]] is caused by the deletion of [[genetic]] material that contains [[elastin]] (ELN) [[gene]] from the region q11.2 of chromosome 7. There are several other genes, apart from ELN gene that contributes to manifestation of [[williams syndrome]] and, therefore, is considered a contiguous [[gene deletion syndrome]].<ref> Merla G, Ucla C, Guipponi M, Reymond A. Identification of additional transcripts in the Williams-Beuren syndrome critical region. Hum Genet. 2002 May. 110(5):429-38.</ref>. <ref> Mari A, Amati F, Mingarelli R, et al. Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Hum Genet. 1995 Oct. 96(4):444-8.</ref> [[LIMK1]] and a number of other genes such as [[GTF1IRD1]], [[GTF2I]], [[NCF1C|NCF1]], [[STX1A]], [[CLIP2]], and [[TFIIA|TFII]]-1 are felt to influence the cognitive profile of Williams syndrome.<ref>assabehji M, Metcalfe K, Fergusson WD, et al. LIM-kinase deleted in Williams syndrome. Nat Genet. 1996 Jul. 13(3):272-3.</ref> Some other genes are considered for manifestation of conditions such as elevated [[calcium]], [[glucose]] [[metabolism]], and [[hypertension]].
The deleted region includes more than 20 [[gene]]s, and researchers believe that the loss of several of these genes probably contributes to the characteristic features of this disorder. {{Gene|CLIP2}}, [[Elastin|ELN]], {{Gene|GTF2I}}, {{Gene|GTF2IRD1}}, and {{Gene|LIMK1}} are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ''ELN'' gene, which codes for the protein [[elastin]], is associated with the connective-tissue abnormalities and cardiovascular disease (specifically [[Aortic valve stenosis|supravalvular aortic stenosis]] (SVAS) and [[Pulmonary valve stenosis|supravalvular pulmonary stenosis]] (SVPS)) found in many people with this syndrome. Studies suggest that deletion of ''LIMK1'', ''GTF2I'', ''GTF2IRD1'', and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, there is evidence that the loss of several of these genes, including ''CLIP2'', may contribute to the unique behavioral characteristics, mental retardation, and other cognitive difficulties seen in Williams syndrome.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
This syndrome is rare and occurrs in fewer than 1 in 7,500 live births.
The [[incidence]] of Williams syndrome is approximately 1 per 75,000 individuals worldwide.<ref>"Morris CA, Braddock SR, COUNCIL ON GENETICS. Health Care Supervision for Children With Williams Syndrome. Pediatrics 2020; 145.</ref> Williams syndrome is considered for about 6% of all [[genetic]] cases of [[Developmental abnormality|developmental]] [[disability]].<ref>Stromme, P.; Bjomstad, P. G.; Ramstad, K. (2002). "Prevalence Estimation of Williams Syndrome". Journal of Child Neurology. 17 (4): 269–71.</ref> William syndrome affects male and female in equal numbers and infants of any [[race]] may be affected.
OR
 
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
 
OR
 
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
 
 
 
Patients of all age groups may develop [disease name].
 
OR
 
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
 
OR
 
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
 
OR
 
[Chronic disease name] is usually first diagnosed among [age group].
 
OR
 
[Acute disease name] commonly affects [age group].
 
 
 
There is no racial predilection to [disease name].
 
OR
 
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
 
 
 
[Disease name] affects men and women equally.
 
OR
 
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
 
 
 
The majority of [disease name] cases are reported in [geographical region].
 
OR
 
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].


==Risk Factors==
==Risk Factors==
There are no established risk factors for [disease name].
There are no established [[Risk factor|risk factors]] for [[Williams syndrome]].
 
OR
 
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.


==Screening==
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
There is insufficient [[evidence]] to recommend routine [[screening]] for Williams syndrome.
 
OR
 
According to the [guideline name], screening for [disease name] is not recommended.
 
OR
 
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
Common complications of Williams syndrome include:
 
OR
 
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
 
OR


Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
*[[Cardiovascular disease]]
*[[Failure to thrive]]
*[[Connective tissue changes]]
*[[Endocrine]] abnormalities
There is no significant reduction in [[life expectancy]] in children diagnosed with Williams syndrome unless there is any significant [[heart]] condition or problems in the [[kidney]].


==Diagnosis==
==Diagnosis==
The clinical diagnosis of Williams syndrome can be made in early childhood based on characteristic facial features. However, the [[diagnosis]] of Williams syndrome is confirmed by [[genetic]] testing ([[fluorescent in situ hybridization]]) that can detect [[Deletion (genetics)|deletion]] of one [[elastin]] [[gene]] on [[chromosome]] 7.<ref>Lowery MC, Morris CA, Ewart A, et al. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am J Hum Genet 1995; 57:49.</ref>
===Symptoms===
===Symptoms===
It is characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers, coupled with unpredictably occurring negative outbursts; [[mental retardation]] coupled with unusual (for persons who are diagnosed as mentally retarded)  [[language]] skills; a love for music; and cardiovascular problems, such as [[supravalvular aortic stenosis]] and transient [[hypercalcaemia]].
The hallmark feature of Williams syndrome is typical 'elfin' facies (upturned nose, wide forehead, and small teeth). A positive history of [[congenital heart disease]] and [[neuro-developmental delay]] is suggestive of Williams syndrome. Williams syndrome can be manifested with various non- specific complains such as poor growth, short stature, muscle weakness, hyperflexible joints, intellectual disability, visual disturbances, chronic ear infections or hearing loss, dental abnormalities. <ref name="pmid20089974">{{cite journal| author=Pober BR| title=Williams-Beuren syndrome. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 3 | pages= 239-52 | pmid=20089974 | doi=10.1056/NEJMra0903074 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20089974  }} </ref> <ref name="pmid20393184">{{cite journal| author=Game X, Panicker J, Fowler CJ| title=Williams-Beuren syndrome. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 15 | pages= 1449; author reply 1450 | pmid=20393184 | doi=10.1056/NEJMc1001965 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20393184  }} </ref>


Williams syndrome shares some features with [[autism]] (such as difficulty understanding the [[theory of mind|state of mind of conversational partners]]<ref>"Rare Disorder Offers Fresh Insight into Language" by Rhitu Chatterjee. National Public Radio. 10 Jul 2006 (text only). [http://www.npr.org/templates/story/story.php?storyId=5545504]</ref>) and [[Fetal alcohol syndrome]] (e.g., certain facial features, possible mental retardation, and negative potential outbursts),<ref>CDC. (2004). ''Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis''. Can be downloaded at http://www.cdc.gov/fas/faspub.htm</ref> although persons with Williams generally possess very good social skills, such that this condition is sometimes called "cocktail-party syndrome".  There also appears to be a higher prevalence of left-handedness and [[ocular dominance|left-eye dominance]] in those with Williams,<ref>Van Strien JW, Lagers-Van Haselen GC, Van Hagen JM, De Coo IF, Frens MA, Van Der Geest JN. "Increased prevalences of left-handedness and left-eye sighting dominance in individuals with Williams-Beuren syndrome." ''J Clin Exp Neuropsychol.'' 2005 Nov;27(8):967-76. PMID 16207621.</ref> and cases of absolute pitch appear to be significantly higher amongst those with the condition.<ref name="Sacks1995">{{cite journal | first=Oliver | last=Sacks | year=1995 | month=May | title=Musical Ability | journal=Science | volume=268 | issue=5211 | pages=621&ndash;622}}</ref>
===Physical Examination===
Patients with Williams syndrome usually have typical 'elfin facies' in appearance. Physical examination of patients with Williams syndrome is usually remarkable for characteristic cardiac lesion such as supravalvar [[aortic]] [[stenosis]] (SVAS), pulmonary stenosis and mitral valve regurgitation along with arterial hypertension.


===Physical Examination===
On physical examination, [[ocular]] findings in Williams syndrome can include [[strabismus]], a [[stellate iris]], [[cataract]] or [[retinal]] [[vascular]] [[tortuosity]]. Audiological evaluation may report  [[Sensorineural hearing loss|sensorineural]] [[hearing loss]] in some patient. Other findings include [[Joint (anatomy)|joint]] [[hyperelasticity]], [[Contracture|contractures]], [[kyphoscoliosis]], and [[lordosis]] along with generalised [[hypotonia]].
====Neurologic====
<ref> Bruno E, Rossi N, Thuer O, et al. Cardiovascular findings, and clinical course, in patients with Williams syndrome. Cardiol Young. 2003 Dec. 13(6):532-6. </ref>
=====Relativity and perception=====
Another symptom of Williams syndrome is lack of [[depth perception]] and an inability to visualize how different parts assemble into larger objects (in assembling jigsaw puzzles, for example). This problem is caused by a defect in the [[brain]] that creates a sparsity of tissue in the visual systems of the brain. When asked to perform tasks involving spatial relations, with their brains scanned by [[Functional magnetic resonance imaging|fMRI]], people with Williams Syndrome showed weaker activity in the dorsal area of the brain, which is along the top and back of the brain and associated with vision and spatial relations. (fMRI measures brain activity by measuring blood flow through different parts of the brain.)


When asked to copy a picture, those with Williams Syndrome drew the small details while those diagnosed with Down Syndrome drew the big picture. (Navon Task)<ref>Bihrle, A. M., Bellugi, U., Delis, D., and Marks, S. (1989) Seeing either the forest or the trees: Dissociation in visual processing. Brain and Cognition, 11:37–49
<br>
Cited by
*[http://nasw.org/finn/ws.html Different Minds - Robert Finn]
*[http://mokk.bme.hu/Members/hp/otka/docs/lukacs_dissertation.doc Language Abilities in Williams Syndrome - Agnes Luckacks]
*[http://www.psyc.bbk.ac.uk/research/DNL/personalpages/Annaz_thesis_2006.pdf The Development of Visuo-spatial Processing in children with Autism, Down Syndrome, and Williams Syndrome - Dagmara Annaz]</ref>
===Laboratory Findings===
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].


OR
Laboratory findings consistent with the diagnosis of Williams syndrome include [[elevated calcium level]] with [[hypercalciuria]] <ref> Sindhar S, Lugo M, Levin MD, et al. Hypercalcemia in Patients with Williams-Beuren Syndrome. J Pediatr 2016; 178:254. </ref>, mild [[thyroid]]-stimulating [[hormone]] elevation with normal [[thyroxine]] T4 (sub-clinical [[hypothyroidism]] in 5 to 10 percent ) <ref> Kim YM, Cho JH, Kang E, et al. Endocrine dysfunctions in children with Williams-Beuren syndrome. Ann Pediatr Endocrinol Metab 2016; 21:15. </ref>, and [[abnormal glucose tolerance test]] in 60 to 75 percent. <ref> Pober BR, Wang E, Caprio S, et al. High prevalence of diabetes and pre-diabetes in adults with Williams syndrome. Am J Med Genet C Semin Med Genet 2010; 154C:291.</ref>
 
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
 
OR
 
[Test] is usually normal among patients with [disease name].
 
OR
 
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
 
OR
 
There are no diagnostic laboratory findings associated with [disease name].


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].


OR
An ECG may be helpful to look for any [[cardiac]] [[anomalies]] such as [[Septal defect|septal]] defects that may be related to Williams syndrome.
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR


There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
There are no x-ray findings associated with Williams syndrome. However, an x-ray may be helpful to look for associated [[anomalies]] with Williams syndrome.


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
OR


Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
[[Renal]] [[ultrasound]] may be helpful in the diagnosis of Williams syndrome. Findings on renal ultrasound suggestive of Williams syndrome include [[bladder diverticula]], [[ectopic]] or [[Horseshoe kidney|horseshoe]] kidney, and renal [[aplasia]] or [[hypoplasia]]. [[Nephrocalcinosis]] secondary to [[hypercalciuria]] is detected in approximately 5 to 10 percent of patients undergoing [[renal]] [[ultrasound]]. <ref> Ingelfinger JR, Newburger JW. The spectrum of renal anomalies in patients with Williams syndrome. J Pediatr 1991; 119:771. </ref>
 
OR
 
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
There are no [[CT-scans|CT]] scan findings associated with Williams syndrome.
 
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
There are no [[MRI]] findings associated with Williams syndrome.
 
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
There are no other imaging findings associated with Williams syndrome.
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].


OR
Other diagnostic studies for Williams syndrome include audiologic evaluation, which demonstrates high tone [[Sensorineural hearing loss|sensorineural]] [[hearing loss]], and [[ophthalmic]] evaluation, which demonstrates [[strabismus]] and [[Refractive error|refractive]] errors.


[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
==Treatment==
 
Based on  2020 American Academy of Pediatrics (AAP) healthcare supervision guidelines for Williams Syndrome, the approach to the management of Williams syndrome consists of 3 major steps:<ref name="pmid19097873">{{cite journal| author=Lacroix A, Pezet M, Capel A, Bonnet D, Hennequin M, Jacob MP | display-authors=etal| title=[Williams-Beuren syndrome: a multidisciplinary approach]. | journal=Arch Pediatr | year= 2009 | volume= 16 | issue= 3 | pages= 273-82 | pmid=19097873 | doi=10.1016/j.arcped.2008.11.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19097873  }} </ref>
OR


Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
*1. Initial evaluation- Our initial evaluation is based upon a comprehensive evaluation that includes [[growth]] measurements; a [[Multidisciplinary Association for Psychedelic Studies|multidisciplinary]] developmental evaluation; thorough [[cardiac]], [[renal]], and [[neurologic]] assessments; and [[laboratory]] [[testing]]. <ref name="pmid31964759">{{cite journal| author=Morris CA, Braddock SR, COUNCIL ON GENETICS| title=Health Care Supervision for Children With Williams Syndrome. | journal=Pediatrics | year= 2020 | volume= 145 | issue= 2 | pages=  | pmid=31964759 | doi=10.1542/peds.2019-3761 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31964759  }} </ref>
*2. Continued [[surveillance]]- Because of the risk of progressive [[disease]], continued [[surveillance]] is recommended throughout the lifetime of the affected person to look for any complications associated with Williams syndrome.
*3. Management of specific conditions- There are no effective [[Pharmacology|pharmacologic]] agents to treat [[arterial]] [[stenosis]]. As a result, approximately one-third of patients with [[cardiovascular]] [[anomalies]] undergo surgical or [[catheter]]-based intervention. Proper [[growth]] of the child with adequate [[nutrition]] need to be accessed. [[Ophthalmic]] evaluation of child needed for any [[Visual disturbance|visual]] disturbances. [[Thyroxine]] [[Supplements|supplement]] for [[hypothyroid]] child might be necessary. Proper evaluation and management of any [[ear]] [[Infection|infections]] should be done.


==Treatment==
===Medical Therapy===
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
There is no treatment for Williams syndrome; the mainstay of [[therapy]] is [[supportive care]] and management of specific conditions or [[complications]] related to Williams syndrome.
 
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.


OR


Surgery is the mainstay of treatment for [disease or malignancy].
[[Surgery operation|Surgery]] is the mainstay of treatment for [[supra-valvular]] [[aortic]] [[Aortic stenosis|stenosis]], which is one of the specific condition related to Williams syndrome.


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
There are no established measures for the [[primary prevention]] of Williams syndrome.
 
OR
 
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
There are no established measures for the [[Secondary Prevention|secondary]] [[prevention]] of Williams syndrome.


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


Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
==External links==


==References==
*[http://www.williams-syndrome.org Williams Syndrome Association]
{{Reflist|2}}


== External links ==
* [http://www.williams-syndrome.org Williams Syndrome Association]
<br>
<br>
[[Category:Genetic disorders]]
[[Category:Genetic disorders]]

Latest revision as of 17:53, 5 September 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Synonyms and keywords: Beuren-Williams syndrome; supravalvular aortic stenosis hypercalcemia syndrome; Williams syndrome; Williams-Beuren syndrome; Chromosome 7q11.23 deletion syndrome, 1.5- to 1.8-mb; WMS; WS

Overview

Williams syndrome (also Williams-Beuren syndrome) is a rare genetic disorder characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers, coupled with unpredictably occurring negative outbursts; mental retardation coupled with unusual (for persons who are diagnosed as mentally retarded) language skills; a love for music; and cardiovascular problems, such as supravalvular aortic stenosis and transient hypercalcemia.

Historical Perspective

The syndrome was first identified in 1961 by Dr. J. C. P. Williams of New Zealand.[1]

Classification

There is no established system for the classification of Williams syndrome.

Pathophysiology

It is thought that Williams syndrome is caused by the deletion of genetic material that contains elastin (ELN) gene from the region q11.2 of chromosome 7. There are several other genes, apart from ELN gene that contributes to manifestation of williams syndrome and, therefore, is considered a contiguous gene deletion syndrome.[2]. [3] LIMK1 and a number of other genes such as GTF1IRD1, GTF2I, NCF1, STX1A, CLIP2, and TFII-1 are felt to influence the cognitive profile of Williams syndrome.[4] Some other genes are considered for manifestation of conditions such as elevated calcium, glucose metabolism, and hypertension.

Epidemiology and Demographics

The incidence of Williams syndrome is approximately 1 per 75,000 individuals worldwide.[5] Williams syndrome is considered for about 6% of all genetic cases of developmental disability.[6] William syndrome affects male and female in equal numbers and infants of any race may be affected.

Risk Factors

There are no established risk factors for Williams syndrome.

Screening

There is insufficient evidence to recommend routine screening for Williams syndrome.

Natural History, Complications, and Prognosis

Common complications of Williams syndrome include:

There is no significant reduction in life expectancy in children diagnosed with Williams syndrome unless there is any significant heart condition or problems in the kidney.

Diagnosis

The clinical diagnosis of Williams syndrome can be made in early childhood based on characteristic facial features. However, the diagnosis of Williams syndrome is confirmed by genetic testing (fluorescent in situ hybridization) that can detect deletion of one elastin gene on chromosome 7.[7]

Symptoms

The hallmark feature of Williams syndrome is typical 'elfin' facies (upturned nose, wide forehead, and small teeth). A positive history of congenital heart disease and neuro-developmental delay is suggestive of Williams syndrome. Williams syndrome can be manifested with various non- specific complains such as poor growth, short stature, muscle weakness, hyperflexible joints, intellectual disability, visual disturbances, chronic ear infections or hearing loss, dental abnormalities. [8] [9]

Physical Examination

Patients with Williams syndrome usually have typical 'elfin facies' in appearance. Physical examination of patients with Williams syndrome is usually remarkable for characteristic cardiac lesion such as supravalvar aortic stenosis (SVAS), pulmonary stenosis and mitral valve regurgitation along with arterial hypertension.

On physical examination, ocular findings in Williams syndrome can include strabismus, a stellate iris, cataract or retinal vascular tortuosity. Audiological evaluation may report sensorineural hearing loss in some patient. Other findings include joint hyperelasticity, contractures, kyphoscoliosis, and lordosis along with generalised hypotonia. [10]

Laboratory Findings

Laboratory findings consistent with the diagnosis of Williams syndrome include elevated calcium level with hypercalciuria [11], mild thyroid-stimulating hormone elevation with normal thyroxine T4 (sub-clinical hypothyroidism in 5 to 10 percent ) [12], and abnormal glucose tolerance test in 60 to 75 percent. [13]

Electrocardiogram

An ECG may be helpful to look for any cardiac anomalies such as septal defects that may be related to Williams syndrome.

X-ray

There are no x-ray findings associated with Williams syndrome. However, an x-ray may be helpful to look for associated anomalies with Williams syndrome.

Echocardiography or Ultrasound

Renal ultrasound may be helpful in the diagnosis of Williams syndrome. Findings on renal ultrasound suggestive of Williams syndrome include bladder diverticula, ectopic or horseshoe kidney, and renal aplasia or hypoplasia. Nephrocalcinosis secondary to hypercalciuria is detected in approximately 5 to 10 percent of patients undergoing renal ultrasound. [14]

CT scan

There are no CT scan findings associated with Williams syndrome.

MRI

There are no MRI findings associated with Williams syndrome.

Other Imaging Findings

There are no other imaging findings associated with Williams syndrome.

Other Diagnostic Studies

Other diagnostic studies for Williams syndrome include audiologic evaluation, which demonstrates high tone sensorineural hearing loss, and ophthalmic evaluation, which demonstrates strabismus and refractive errors.

Treatment

Based on 2020 American Academy of Pediatrics (AAP) healthcare supervision guidelines for Williams Syndrome, the approach to the management of Williams syndrome consists of 3 major steps:[15]

Medical Therapy

There is no treatment for Williams syndrome; the mainstay of therapy is supportive care and management of specific conditions or complications related to Williams syndrome.

Surgery

Surgery is the mainstay of treatment for supra-valvular aortic stenosis, which is one of the specific condition related to Williams syndrome.

Primary Prevention

There are no established measures for the primary prevention of Williams syndrome.

Secondary Prevention

There are no established measures for the secondary prevention of Williams syndrome.

References

  1. ↑ "The Gregarious Brain," by David Dobbs. The New York Times, July 8, 2007. [1]
  2. ↑ Merla G, Ucla C, Guipponi M, Reymond A. Identification of additional transcripts in the Williams-Beuren syndrome critical region. Hum Genet. 2002 May. 110(5):429-38.
  3. ↑ Mari A, Amati F, Mingarelli R, et al. Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Hum Genet. 1995 Oct. 96(4):444-8.
  4. ↑ assabehji M, Metcalfe K, Fergusson WD, et al. LIM-kinase deleted in Williams syndrome. Nat Genet. 1996 Jul. 13(3):272-3.
  5. ↑ "Morris CA, Braddock SR, COUNCIL ON GENETICS. Health Care Supervision for Children With Williams Syndrome. Pediatrics 2020; 145.
  6. ↑ Stromme, P.; Bjomstad, P. G.; Ramstad, K. (2002). "Prevalence Estimation of Williams Syndrome". Journal of Child Neurology. 17 (4): 269–71.
  7. ↑ Lowery MC, Morris CA, Ewart A, et al. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am J Hum Genet 1995; 57:49.
  8. ↑ Pober BR (2010). "Williams-Beuren syndrome". N Engl J Med. 362 (3): 239–52. doi:10.1056/NEJMra0903074. PMID 20089974.
  9. ↑ Game X, Panicker J, Fowler CJ (2010). "Williams-Beuren syndrome". N Engl J Med. 362 (15): 1449, author reply 1450. doi:10.1056/NEJMc1001965. PMID 20393184.
  10. ↑ Bruno E, Rossi N, Thuer O, et al. Cardiovascular findings, and clinical course, in patients with Williams syndrome. Cardiol Young. 2003 Dec. 13(6):532-6.
  11. ↑ Sindhar S, Lugo M, Levin MD, et al. Hypercalcemia in Patients with Williams-Beuren Syndrome. J Pediatr 2016; 178:254.
  12. ↑ Kim YM, Cho JH, Kang E, et al. Endocrine dysfunctions in children with Williams-Beuren syndrome. Ann Pediatr Endocrinol Metab 2016; 21:15.
  13. ↑ Pober BR, Wang E, Caprio S, et al. High prevalence of diabetes and pre-diabetes in adults with Williams syndrome. Am J Med Genet C Semin Med Genet 2010; 154C:291.
  14. ↑ Ingelfinger JR, Newburger JW. The spectrum of renal anomalies in patients with Williams syndrome. J Pediatr 1991; 119:771.
  15. ↑ Lacroix A, Pezet M, Capel A, Bonnet D, Hennequin M, Jacob MP; et al. (2009). "[Williams-Beuren syndrome: a multidisciplinary approach]". Arch Pediatr. 16 (3): 273–82. doi:10.1016/j.arcped.2008.11.011. PMID 19097873.
  16. ↑ Morris CA, Braddock SR, COUNCIL ON GENETICS (2020). "Health Care Supervision for Children With Williams Syndrome". Pediatrics. 145 (2). doi:10.1542/peds.2019-3761. PMID 31964759.

External links


da:Williams syndrom de:Williams-Beuren-Syndrom it:Sindrome di Williams-Beuren he:תסמונת ויליאמס hu:Williams-szindróma nl:Williams-syndroom

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