Williams syndrome (7q11.23 deletion, ELN gene): features and genetics

Williams syndrome is a multisystem genetic condition. The NHS Genomics Education Programme describes mild to moderate intellectual disability, a friendly and outgoing personality, poor visuospatial skills and an increased risk of narrowing of the main artery leaving the heart. Facial features change over time and tend to become more pronounced with age: a round face that elongates, full cheeks, a wide mouth, a flat nasal bridge and widely spaced, underdeveloped teeth.

Many body systems can be involved. The programme lists cardiovascular disease, with supravalvar aortic stenosis in 75% and almost any artery liable to narrow; high blood pressure; connective tissue features such as hernias, joint laxity and soft lax skin; growth deficiency and persistent short stature; feeding difficulties, reflux and constipation in infancy; kidney and urinary anomalies; spinal curvature; endocrine anomalies including raised calcium, underactive thyroid and early puberty; and behavioural and sensory issues such as sound sensitivity, anxiety, phobias, ADHD and sleep disorders.

The Williams Syndrome Foundation notes that no single treatment applies, but therapies such as physiotherapy, occupational therapy, speech therapy, music therapy and psychological therapy help with particular issues, that physical problems such as heart conditions can be treated, and that the earlier help starts the better the prospects.

Unlike many conditions on this site, Williams syndrome is not caused by a change inside one gene. It is a microdeletion, the loss of a small stretch of chromosome 7 at position 7q11.23. People with it have one copy rather than two of 26 to 28 genes, including ELN, which makes elastin. The NHS Genomics Education Programme says loss of ELN is associated with the connective tissue problems and explains some of the facial features, cardiac anomalies and orthopaedic difficulties, while research continues on the contributions of the other genes.

The deletion can be identified by whole genome sequencing, by microarray, or by a fluorescence in situ hybridisation (FISH) probe designed for 7q11.23. The programme points out that significantly smaller or larger deletions in this region cause different medical problems, which is why the exact extent matters.

The Williams Syndrome Foundation answers a common worry directly: nothing a parent has done or not done caused the condition, which it describes as a randomly occurring genetic condition. The NHS Genomics Education Programme says most cases are de novo, arising from a new microdeletion in the egg or sperm, with typically no family history.

The foundation says it is extremely unlikely but not impossible that another family member or later child will have it. The one genetic route is a parent having a patch of ovary or testis cells with the deletion, which could produce more than one egg or sperm with it. The programme gives the recurrence risk for unaffected parents as less than 1%, due to germline mosaicism or a predisposing structural variant such as an inversion. A geneticist may sometimes test the parents to look for such a change.

A person with Williams syndrome who has children has a 50% chance of passing on the microdeletion with each pregnancy, and the programme says testing in pregnancy or pre-implantation genetic testing may be discussed.

The programme says management of children is complex and delivered by a multidisciplinary team that often includes clinical genetics, community paediatrics, ophthalmology, audiology, cardiology, endocrinology and dietetics, and that a baseline kidney ultrasound is recommended. Meetings that bring together health, social care and education, called Team Around the Child or Family, can help to coordinate care.

The Williams Syndrome Foundation says that if a child is diagnosed because of another symptom, they should be referred to a cardiologist to check for a heart problem, and it publishes clinical guidelines that parents can share with doctors. It notes that about 1 in 30 GPs ever meets someone with Williams syndrome, so a doctor not having come across it is not unusual.

The Williams Syndrome Foundation is the UK charity for the condition. For new diagnoses it describes a regional network of families, information and social events, a magazine and access to a panel of medical experts, and it asks for the genetic test result before membership because misdiagnosis occurred before standard genetic testing. It also recognises that families may feel overwhelmed, anxious or even relieved after waiting for an explanation, and points to wellbeing support for parents.