What is Williams syndrome?

From the Guidelines

Williams syndrome (WS) is a multisystem genetic disorder caused by a deletion of part of chromosome 7, characterized by distinct facial features, cardiovascular disease, intellectual disability, and a unique cognitive profile.

Key Characteristics

• The deleted portion of chromosome 7q11.23 contains 26 to 28 genes, including the ELN gene, which codes for the structural protein elastin 1.
• WS is present at birth with a prevalence of 1 in 7500 and affects boys and girls equally 1.
• Children with WS usually come to the attention of pediatricians during infancy or early childhood.
• The syndrome is characterized by:
  • Dysmorphic facies (100%)
  • Cardiovascular disease (80%), most commonly supravalvular aortic stenosis (SVAS)
  • Intellectual disability (75%)
  • A characteristic cognitive profile (90%)
  • Idiopathic hypercalcemia (15% to 45%) ### Clinical Manifestations The clinical manifestations of WS can be anticipated and managed by pediatricians using knowledge of the natural history of the syndrome, as outlined in Table 1 2.
• Ocular and visual problems, such as esotropia and hyperopia
• Auditory problems, such as recurrent otitis media and hypersensitivity to sound
• Dental problems, such as malocclusion and microdontia
• Cardiovascular problems, such as SVAS and hypertension
• Genitourinary problems, such as structural anomalies and enuresis
• Gastrointestinal problems, such as feeding difficulties and constipation
• Integumentary problems, such as soft, lax skin and inguinal hernia
• Musculoskeletal problems, such as joint hypermobility and joint contractures
• Calcium and endocrine problems, such as hypercalcemia and hypothyroidism
• Neurologic problems, such as hyperactive deep tendon reflexes and Chiari I malformation
• Cognitive and behavioral problems, such as developmental delay, intellectual disability, and anxiety disorder ### Management A medical genetics evaluation is recommended to discuss the clinical manifestations, natural history, and recurrence risks for parents and other family members 1.
• 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.
• The recommendations for managing WS reflect review of the current literature and the consensus of physicians with expertise in the care of individuals with WS 3.

From the Research

Definition and Prevalence of Williams Syndrome

• Williams syndrome (WS) is a relatively rare microdeletion disorder that occurs in as many as 1:7,500 individuals 4.
• It is caused by a hemizygous deletion of approximately 25-27 genes on the 7th chromosome (7q11.23) 4, 5, 6.

Characteristics and Features of Williams Syndrome

• The disorder affects multiple systems, with cardinal features including cardiovascular disease, a distinctive craniofacial appearance, and a specific cognitive and behavioural profile 4.
• Individuals with WS often experience intellectual disability, hypersociability, and anxiety 4, 7, 5.
• They may also have atypical facial characteristics, such as medial eyebrow flair, epicanthal folds, and a upturned nose 5.
• Cardiac and renal abnormalities, as well as hypertension, are common in individuals with WS 4, 5, 6.

Cognitive and Behavioural Profile

• Individuals with WS tend to have an uneven cognitive-linguistic profile, with relative strengths in some aspects of language and face processing, but significant delays in visuospatial skills 5, 8, 6.
• They often exhibit overly friendly behaviour, but may also experience nonsocial anxieties and lack social judgement skills 7, 5, 6.
• Cognitive skills are typically in the mild to moderately delayed range, with some individuals achieving near normal scores in certain areas, such as face processing 5, 6.

Genetic Basis and Research

• The deletion of specific genes, such as ELN, GTF2I, and GTF2IRD1, has been linked to the vascular and connective tissue features of WS, as well as intellectual ability and social functioning 4.
• Further research is needed to understand the mechanism by which these deletions contribute to clinical outcomes and to identify the factors responsible for phenotypic variability in WS 4, 7.