From the Guidelines
Williams syndrome is a rare genetic disorder caused by the deletion of about 26 genes on chromosome 7, affecting approximately 1 in 7,500 people, and is characterized by distinctive facial features, cardiovascular problems, developmental delays, and a unique personality profile. According to the American Academy of Pediatrics 1, Williams syndrome is a multisystem disorder that is present at birth and affects boys and girls equally. The deleted portion of chromosome 7q11.23 contains 26 to 28 genes, including the ELN gene that codes for the structural protein elastin, which is an important component of the elastic fibers found in the connective tissue of many organs.
Key Characteristics
- Dysmorphic facies (100%)
- Cardiovascular disease (80%; most commonly supravalvular aortic stenosis [SVAS])
- Intellectual disability (75%)
- Characteristic cognitive profile (90%)
- Idiopathic hypercalcemia (15% to 45%)
- The condition is typically diagnosed through genetic testing that confirms the chromosome 7 deletion, and while there is no cure, supportive therapies can significantly improve quality of life 1.
Medical Management
- Monitoring for cardiovascular issues
- Addressing developmental delays through early intervention
- Treating associated conditions like hypercalcemia, hypertension, and joint problems
- Using knowledge of the clinical manifestations and natural history of WS to anticipate medical problems and educate the family 1.
Growth and Development
- Growth parameters should be plotted on WS growth charts
- Children with WS typically have decreased fat stores, but obesity may become a problem in teenagers and adults
- Microcephaly is present in one-third of affected individuals 1.
From the Research
Definition and Prevalence of Williams Syndrome
- Williams syndrome (WS) is a neurodevelopmental genetic disorder with a prevalence of approximately 1 in 7500 2.
- It is caused by a hemizygous deletion of approximately 28 genes on the 7th chromosome (7q11.23), including the elastin allele 2, 3.
Characteristics and Symptoms
- Individuals with WS have atypical facial characteristics, including medial eyebrow flair, epicanthal folds, upturned nose, elongated philtrum, and full lips 2.
- Infants typically experience constipation and colic, while cardiac and renal abnormalities, as well as hypertension, are common 2.
- Individuals with WS are at increased risk for hearing and vision difficulties, and gastrointestinal difficulties such as constipation and diverticulitis are common 2.
- Joint abnormalities are observed in both children and adults with WS, and individuals with WS are overly friendly yet can experience nonsocial anxieties 2.
Cognitive and Developmental Aspects
- Cognitive skills are typically in the mild to moderately delayed range, with relative strengths in some aspects of language and face processing 2, 4, 5.
- Visuospatial skills are significantly delayed, and individuals with WS may have impaired visual-spatial constructive cognition 2, 3, 4.
- The syndrome is characterized by a distinctive cognitive profile, with strengths in social and language abilities, but weaknesses in visuospatial cognition 4, 5.
Genetic and Molecular Aspects
- WS is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23, including the elastin gene and other novel genes such as WS-betaTRP, WS-bHLH, and BCL7B 3.
- The common WS deletion region has been characterized, and fluorescence in situ hybridization (FISH) analysis can be used to detect the deletion 3, 6.