What are the other Names for this Condition? (Also known as/Synonyms)

• BAZ1B
• Williams-Beuren Syndrome Chromosomal Region 9 Protein
• Williams-Campbell Syndrome

What is Williams Syndrome? (Definition/Background Information)

• Williams Syndrome is a genetic disorder caused by the deletion of few gene copies on chromosome 7, which involves the elastin gene. The disorder affects multiple organ systems
• It is characterized by facial anomalies, cardiovascular anomalies, high blood calcium, neuro-developmental and behavioral disorders. These anomalies and defects may be present at birth or may develop later in life
• Williams Syndrome cannot be cured. The treatment is mostly symptomatic (avoiding complications) and therapeutic. The prognosis is based on the specific condition and symptoms of each individual. Those with severe cardiac anomalies may not have a positive outcome

Who gets Williams Syndrome? (Age and Sex Distribution)

• Williams Syndrome is a genetic condition with an incidence rate of about 1 in 7500
• The incidence of deletion of genes is similar between men and women, but the cardiovascular events may manifest early in males
• Some clinical manifestations may vary according to races, for example, pulmonary artery stenosis is common among the Chinese population, while cardiovascular events are very minimal in Greece

What are the Risk Factors for Williams Syndrome? (Predisposing Factors)

• There are no specific risk factors that have been identified
• Williams Syndrome does not seem to be transmitted through familial inheritance

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Williams Syndrome? (Etiology)

• The main and only cause of Williams Syndrome is the deletion of a set of genes on chromosome 7
• Other than elastin gene, a few other genes are also being investigated, such as LIMK1, GTF1IRD1, and GTF2I, in the clinical manifestations of Williams Syndrome
• Also, since a number of other genes are also deleted along with the elastin gene, this condition is considered as a contiguous gene deletion syndrome
• The facial morphology and cardiovascular anomalies are attributed to elastin gene insufficiency

What are the Signs and Symptoms of Williams Syndrome?

The signs and symptoms associated with Williams Syndrome are multifarious and these include:

• Growth delay and short stature in children
• Recurrent middle ear infection in children
• Congenital heart disease
• Functional problems such as delay in toilet training, increased urinary frequency and daytime wetting
• Glucose intolerance and overt diabetes mellitus by the age of 20 years: By age 30 years, a significant number of individuals have either prediabetes or fully-developed diabetes that often requires treatment
• Low thyroid hormone
• Connective tissue abnormalities such as laxity of joints, hernias, diverticulosis in colon
• Delay in language development; nearly 50% children with Williams Syndrome have attention deficit disorder (ADD)
• Visual-spatial problems that impact one’s daily life, with difficulties in handwriting, drawing, and gait disturbance (especially on uneven or sandy surfaces)
• Facial features - short upturned nose, flat nasal bridge, long philtrum, flat cheeks, wide mouth, full lips, dental malocclusion and widely spaced teeth, short jaw, and periorbital fullness. A stellate, lacy pattern of the iris can be observed in children with blue eyes
• The voice may be hoarse
• Anxiety is a very common symptom
• A significant number of individuals with Williams Syndrome have specific phobias, such as fear of closed spaces, fear of heights, and fear of loud noises

Cardiovascular anomalies manifest as narrowing of the large and medium sized arteries, due to loss of elasticity. The commonly affected blood vessels are the aorta (a large blood vessel carrying blood from heart to other parts of the body), specifically above the aortic valve and the pulmonary artery (blood vessel carrying blood from the heart to the lungs). Nonetheless, narrowing of the descending aorta, intracranial arteries, and renal arteries have been reported.

How is Williams Syndrome Diagnosed?

The diagnosis may involve a complete evaluation of one’s medical history along with a thorough physical exam. The following tests may be performed in individuals suspected of having William Syndrome:

• Fluorescent in situ hybridization (FISH) for the 7q11.23 elastin gene deletion should be performed in patients with suspected Williams Syndrome, in addition to a routine chromosomal analysis (karyotype)
• Echocardiography to rule-out cardiac anomalies
• Renal ultrasound to rule-out anatomic abnormalities and to check for any renal stones, caused by high calcium levels
• Tests to determine blood calcium level, which may be elevated
• Tests to determine creatinine phosphokinase levels, which may be elevated due to underlying inflammation of the muscles
• Thyroid function tests
• The clinical manifestations, such as cardiovascular anomalies and renal cysts, may be evident on an antenatal screening ultrasound

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Williams Syndrome?

Complications associated with Williams Syndrome are:

• Sudden cardiac death: The risk of sudden death due to the narrowing of arteries increases by 25 to 100 folds in individuals with Williams Syndrome, than the general population
• Stroke and hypertension at a younger age
• Gastrointestinal complications, such as colonic diverticulosis, chronic constipation, GERD, etc.
• Mental retardation, short-term memory loss
• Hearing loss
• Presence of kidney stones
• Dental diseases

How is Williams Syndrome Treated?

There is no definitive cure for Williams Syndrome; the treatment depends on the combination of each individual’s signs and symptoms. The main strategy of treatment involves careful monitoring for the development of complications.

• Blood calcium and vitamin D level should be monitored frequently
• Surgical treatment of cardiac anomalies
• Treatment for heart failure and high blood sugar (if any present)
• Treatment of visual abnormalities and hearing loss
• Patients with short stature should be assessed for bone age and may be referred to an endocrinologist for assessment of growth hormone levels
• Thyroid function and glucose tolerance testing should be part of the periodic evaluation
• Monitoring for any signs of precocious puberty
• Speech and language therapy
• Psychological treatment for behavioral issues and anxiety

How can Williams Syndrome be Prevented?

• There are no effective ways to prevent Williams Syndrome, as it is a genetic disorder with sporadic occurrence
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Williams Syndrome? (Outcomes/Resolutions)

• The prognosis of Williams Syndrome depends upon the severity of the signs and symptoms and it varies from one individual to another. The presence of medical complications may result in decreased life spans
• Cardiovascular anomalies are responsible for the mortality in those with Williams Disease
• Patients should be monitored frequently for the development of symptoms, so that they can be addressed and treated early on

Additional and Relevant Useful Information for Williams Syndrome:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/