Williams Syndrome Flashcards
A 4-year-old girl is brought to the pediatrician for developmental evaluation. Her parents report that she has an overly friendly personality, often approaching strangers with ease. On examination, she has a distinctive facial appearance with a broad forehead, a short nose with a bulbous tip, full cheeks, and a wide mouth with prominent lips. She is small for her age and has a heart murmur. Echocardiography reveals supravalvular aortic stenosis. Laboratory tests show elevated serum calcium levels.
What is the most likely diagnosis, and what genetic mutation is associated with this condition?
A. Turner syndrome, SHOX gene mutation
B. Down syndrome, trisomy 21
C. Williams syndrome, deletion on chromosome 7q11.23
D. DiGeorge syndrome, 22q11.2 deletion
E. Noonan syndrome, PTPN11 mutation
Correct Answer: Williams syndrome, deletion on chromosome 7q11.23
Explanation: Williams syndrome is caused by a deletion on chromosome 7q11.23, which includes the elastin (ELN) gene. It is characterized by distinctive facial features (‘elfin facies’), developmental delays, mild to moderate intellectual disability with strong verbal skills, and a friendly, outgoing personality. Supravalvular aortic stenosis is the most common cardiac abnormality, and hypercalcemia is a hallmark metabolic finding, especially in infancy. Genetic testing confirms the diagnosis.
Incorrect Answers:
A. Turner syndrome: This condition affects females and is associated with short stature, lymphedema, and coarctation of the aorta, but not the described facial features or hypercalcemia. B. Down syndrome: Associated with intellectual disability and congenital heart defects, such as atrioventricular septal defects, but not supravalvular aortic stenosis or hypercalcemia. D. DiGeorge syndrome: Involves cardiac defects (e.g., tetralogy of Fallot), hypocalcemia, and thymic hypoplasia, but not the friendly personality or elfin facial features seen in Williams syndrome. E. Noonan syndrome: Involves characteristic facial features, short stature, and pulmonary valve stenosis, but does not present with hypercalcemia or the overly friendly behavior characteristic of Williams syndrome.
What is the genetic cause of Williams syndrome?
Williams syndrome is caused by a deletion on chromosome 7q11.23, which includes the elastin (ELN) gene.
What are the characteristic facial features of Williams syndrome?
Facial features include a broad forehead, short nose with a bulbous tip, small jaw, long philtrum, full cheeks, wide mouth, flat nasal bridge, and prominent lips.
Often described as ‘elfin’ facies.
What electrolyte is abnormally high in Williams syndrome, and how does it present?
Hypercalcemia is a common metabolic feature, especially in infancy, and can present with irritability, constipation, and nephrocalcinosis.
Hypercalcemia in Williams syndrome occurs due to increased sensitivity to vitamin D, though the exact mechanism is not fully understood. It is thought to involve dysregulation of calcium metabolism related to abnormalities in the elastin (ELN) gene or other genes affected by the deletion on chromosome 7q11.23. This heightened sensitivity to vitamin D leads to increased intestinal calcium absorption, resulting in elevated serum calcium levels.
What are common behavioral traits in children with Williams syndrome?
Behavioral traits include emotional liability, strong interest in music, anxiety, and phobias.
These patients tend to have normal verbal skills.
They are extremely friendly.
What are the developmental and intellectual characteristics of Williams syndrome?
Patients often have mild to moderate intellectual disability with strengths in verbal skills and an overly friendly, outgoing personality.
What cardiovascular abnormalities are associated with Williams syndrome?
The most common cardiovascular defect is supravalvular aortic stenosis.
Pulmonary artery stenosis.
Renal artery stenosis.
What are the common musculoskeletal findings in Williams syndrome?
Musculoskeletal findings include joint laxity, scoliosis, and short stature.
What endocrine abnormality is known to be associated with Williams syndrome?
Hypothyroidism.
In Williams syndrome, the primary ophthalmological findings include …?
Strabismus: Misalignment of the eyes is common, which may lead to amblyopia (lazy eye) if untreated.
Hyperopia (farsightedness): Refractive errors, particularly farsightedness, are frequently seen in these patients.
Iris stellate pattern: A distinctive “starburst” pattern in the iris is a hallmark feature, contributing to their characteristic eye appearance.
Visual processing difficulties: While not a direct ophthalmologic finding, patients may have deficits in visual-spatial processing due to neurodevelopmental abnormalities associated with the syndrome.
How is Williams syndrome diagnosed?
Diagnosis is confirmed with genetic testing, such as fluorescence in situ hybridization (FISH) or microarray, to identify the chromosome 7q11.23 deletion.
What is the treatment and management approach for Williams syndrome?
Management includes monitoring and treating cardiovascular abnormalities, addressing hypercalcemia, developmental therapies, and behavioral support.
What is the prognosis for patients with Williams syndrome?
With appropriate medical care and support, many individuals with Williams syndrome can lead productive lives, but they often have lifelong medical and developmental challenges.
