It is a genetic condition with an incidence rate of approximately 1 in 7500 people.
Originally independently described by Williams and Beuren in 1961, Williams syndrome is a rare genetic condition.
This genetic disorder is caused by the deletion of some copies of genes on chromosome 7, which involves the elastin gene.
The disorder affects multiple organ systems.
The incidence of gene deletion is similar between men and women, but cardiovascular events can manifest early in men.
Some clinical manifestations may vary between races, for example, pulmonary artery stenosis is common among the Chinese population, while cardiovascular events are minimal in Greece.
The cause of this genetic abnormality is not known. In most cases, the child with Williams syndrome is the only one in the family and neither parent has passed on the genetic abnormality.
A person with Williams syndrome, however, has a 50% chance of transmitting the condition to their children.
The main and only cause of Williams syndrome is the deletion of a set of genes on chromosome 7.
In addition to the elastin gene, some other genes, such as LIMK1, GTF1IRD1, and GTF2I, are also being investigated in the clinical manifestations of Williams syndrome.
Since several other genes are also deleted along with the elastin gene, this condition is considered a contiguous gene deletion syndrome.
Facial morphology and cardiovascular abnormalities are attributed to elastin gene insufficiency.
Signs and symptoms of Williams syndrome
The signs and symptoms associated with Williams syndrome are multiple:
The clinical manifestations include a distinct facial appearance.
Facial features are generally: short upturned nose, flat nasal bridge, long strainer, flat cheeks, wide mouth, full lips, dental malocclusion and widely spaced teeth, short jaw, and periorbital fullness. The voice may be hoarse.
Children have low birth weight, growth retardation, and short stature in children.
A starry lace pattern of the iris can be seen in children with blue eyes and hyperopic cases.
There is also a sunken chest, the little finger bent inwards.
Motor, psychological and neurological development
Neurodevelopmental problems are seen, such as delayed language development.
Almost 50% of children with Williams syndrome have attention deficit hyperactivity disorder and learning disorders.
Visual-spatial problems in daily life, with difficulties in handwriting and drawing.
They present peculiar phobias, a significant number of people with Williams syndrome have specific phobias, such as fear of closed spaces, fear of heights and fear of loud noises.
Anxiety is a very common symptom.
A characteristic profile of behavior is hypersociability .
There is a delay in psychomotor development and an alteration in gait (especially on uneven or sandy surfaces).
Functional problems, such as delayed toilet training, increased urinary frequency, and problems with sphincter control during the day.
Glucose intolerance and diabetes mellitus is seen and manifests by the age of 20: By the age of 30, a significant number of people have glucose problems or have developed diabetes that often requires treatment.
Middle ear infections are recurrent in children.
Thyroid hormone can cause hypothyroid problems.
A high level of calcium is exhibited in the blood (idiopathic hypercalcemia).
Feeding problems, colic, and kidney abnormalities occur.
Connective tissue abnormalities cause problems such as joint laxity, hernias, diverticulites in the colon.
Cardiovascular abnormalities can be present at birth or can develop later in life.
These manifest as a narrowing of the large and medium arteries, due to the loss of elasticity.
Commonly affected blood vessels are the aorta (a large blood vessel that carries blood from the heart to other parts of the body), specifically above the aortic valve, and the pulmonary artery (a blood vessel that carries blood from the heart to the lungs).
However, narrowing of the descending aorta, intracranial arteries, and renal arteries has been reported.
Williams syndrome diagnosis
The diagnosis of Williams syndrome can be complicated by the variability in symptoms and effects of the disease.
However, the group of symptoms that generally occur can be rounded to determine the diagnosis.
The diagnosis may involve a complete evaluation of one’s medical history along with a complete physical examination.
The following tests can be performed on individuals suspected of having William syndrome:
- Fluorescent in situ hybridization for the deletion of the elastin 7q11.23 gene should be performed in patients with suspected Williams syndrome, in addition to a routine chromosome analysis (karyotype).
- Echocardiography to rule out heart abnormalities.
- Kidney ultrasound to rule out anatomical abnormalities and to check for kidney stones caused by high calcium levels.
- Tests to determine the level of calcium in the blood, which may be elevated.
- Tests to determine creatinine phosphokinase levels, which may be elevated due to underlying inflammation of the muscles.
- Thyroid function tests.
Clinical manifestations, such as cardiovascular abnormalities and kidney cysts, may be apparent on a prenatal ultrasound.
Many clinical conditions can have similar signs and symptoms.
The doctor may perform additional tests to rule out other clinical conditions in order to make a definitive diagnosis.
Possible complications of Williams syndrome
Complications associated with Williams syndrome are generally:
- Sudden cardiac death. The risk of sudden death due to narrowing of the arteries increases 25 to 100 times in people with Williams syndrome, compared to the general population.
- Stroke and hypertension at an earlier age.
- Gastrointestinal complications, such as colonic diverticulosis, chronic constipation, gastroesophageal reflux disease, among others.
- Mental retardation, short-term memory loss.
- Hearing loss.
- Presence of kidney stones.
- Dental disease
Williams syndrome treatment
There is no definitive cure for Williams syndrome, the treatment will depend on the combination of the signs and symptoms of each individual.
The main treatment strategy consists of careful monitoring for the development of complications such as:
- The calcium in the blood and the level of vitamin D should be checked frequently.
- Surgical treatment of cardiac anomalies.
- Treatment for heart failure and high blood sugar (if present).
- Treatment of visual abnormalities and hearing loss.
- Patients with short stature should be evaluated for bone age and may be referred to an endocrinologist to evaluate growth hormone levels.
- Thyroid function and glucose tolerance tests should be part of the regular evaluation.
- Follow up for any signs of precocious puberty.
- Speech and language therapy.
- Psychological treatment for behavior problems and anxiety.
Within treatment, early intervention by multidisciplinary teams should be foreseen.
These are made up of special education professionals, physicians, including the pediatrician, speech therapist, physical therapist, orthodontist, and psychologist, who can assist individuals with Williams syndrome in their development as they grow and support them in lead independent lives as adults.
Williams syndrome prevention
There are no effective ways to prevent Williams syndrome, as it is a genetic disorder with sporadic onset.
If there is a family history of the condition, then genetic counseling will help assess the risks, before planning for a pregnancy.
Active research is currently underway to explore the possibilities of treatment and prevention of inherited and acquired genetic disorders.
Williams syndrome prognosis
The prognosis of Williams syndrome depends on the severity of the signs and symptoms and varies from one individual to another.
The presence of medical complications can result in a shortened lifespan.
Cardiovascular abnormalities are the main culprits for mortality in people with Williams disease.
Patients should be monitored frequently for the development of symptoms so that they can be treated early