Williams syndrome

Williams syndrome is a multisystem genetic condition caused by a microdeletion on one copy of chromosome 7 at position 7q11.23. It results in mild to moderate intellectual disability, a friendly, outgoing personality and an increased chance of supravalvular aortic stenosis.

• Facial features, which change over time and tend to become more pronounced with age:
  • a round face, which elongates over time;
  • epicanthic folds;
  • full cheeks;
  • prominent ears;
  • thick lips;
  • a wide mouth;
  • a flat nasal bridge;
  • a bulbous nasal tip;
  • widely spaced, underdeveloped teeth; and
  • a stellate pattern to the iris.
• Mild to moderate learning difficulties:
  • happy, friendly, outgoing personality; and
  • poor visuospatial skills.
• Cardiovascular disease:
  • supravalvar aortic stenosis occurs in 75% of affected individuals;
  • peripheral pulmonic stenosis is common in infancy but improves with time;
  • almost any artery can be narrowed; and
  • hypertension can be present.
  • Connective tissue anomalies:
    • hernias;
    • joint laxity;
    • soft lax skin;
    • bowel and/or bladder diverticula; and
    • rectal prolapse.
• Pre- and postnatal growth deficiency and persistent short stature.
• Gastrointestinal issues: feeding difficulties (especially in infancy), reflux, constipation.
• Genitourinary: structural anomalies, nephrocalcinosis, enuresis.
• Musculoskeletal: kyphosis, scoliosis, lordosis.
• Neurological: Chiari I malformation (type 1).
• Endocrine anomalies:
  • idiopathic hypercalcemia;
  • hypercalciuria;
  • hypothyroidism;
  • early puberty; and
  • diabetes mellitus.
• Behavioural and sensory difficulties:
  • hypersensitivity to sound;
  • anxiety and specific phobias;
  • ADHD; and
  • sleep disorders.

Williams syndrome is caused by a 1.5–1.8 megabase at chromosome position 7q11.23. This means that individuals with Williams syndrome have one, rather than the usual two, copies of 26 to 28 genes, including the elastin (ELN) gene. Research is ongoing to determine the relative contributions of each gene. For example, loss of ELN is associated with the connective tissue and explains some of the facial features, cardiac anomalies and orthopaedic difficulties often present in those with Williams syndrome. This microdeletion can be identified using microarray or by using a fluorescent in situ hybridisation (FISH) probe created specifically to identify the 7q11.23 deletion.

Note that significantly smaller or larger deletions in this region can cause different medical problems.

For information about testing, see Presentation: Clinical suspicion of Williams syndrome.

Most cases of Williams syndrome occur de novo, due to a new microdeletion in the egg or sperm. Typically, there is no family history. If an individual with Williams syndrome has children, there is a 50% chance of passing the microdeletion on in each pregnancy. Individuals with Williams syndrome may wish to discuss reproductive options, which could include testing in pregnancy or IVF with genomic testing.

Management of children with Williams syndrome is complex and should be delivered via a multidisciplinary team. Detailed suggested approaches have been published by several authors – see the resources list below. Specialty involvement often includes clinical genetics, community paediatrics, ophthalmology, audiology, cardiology, endocrinology and dietetics. Baseline renal ultrasound is recommended.

In view of the number of professionals involved, Team Around the Child and/or Team Around the Family meetings can help with communication and coordinating care between health, social care and education.

For clinicians

• GeneReviews: Williams syndrome
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NHS England: National Genomic Test Directory
• National Organisation for Rare Disease: Williams syndrome
• Williams Syndrome Guideline Development Group and Dyscerne: Management of Williams syndrome: A clinical guideline

References:

• Morris CA, Braddock Stephen R, Council on Genetics and others. ‘Health care supervision for children with Williams syndrome’. Pediatrics 2020: volume 145, issue 2. DOI: 10.1542/peds.2019-3761

For patients

• Council for Disabled Children: The Information, Advice and Support Services Network
• Gov.uk Guidance: SEND code of practice, 0 to 25 years
• Gov.uk Guidance: Disability Living Allowance (DLA) for children
• Mencap: Williams syndrome
• Williams Syndrome Foundation