WILLIAMS SYNDROME

WILLIAMS SYNDROME - Gene S.Fisch, PhD
BASICS
DESCRIPTION
• Williams syndrome is an unusual multisystem neurodevelopmental disorder typified by characteristic craniofacial features, mild microcephaly, mild to moderate mental retardation with a distinctive cognitive-behavioral profile, connective tissue abnormalities, growth retardation, supravalvular aortic stenosis, peripheral pulmonary stenosis, renal artery stenosis, limited joint movement, and transient hypercalcemia.
• Occurrence is sporadic, although familial autosomal dominant cases have been infrequently reported.
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Musculoskeletal; Nervous; Renal/Urologic
• Synonym(s): Williams-Beuren syndrome; Fanconi-type idiopathic infantile hypercalcemia; Elfin facies syndrome
ALERT
Pediatric Considerations
Infantile hypercalcemia
Pregnancy Considerations
Patient and family should receive genetic evaluation and counseling, as prenatal diagnosis is available.
GENERAL PREVENTION
Genetic counseling and evaluation, especially among high-functioning patients, about pregnancies. Prenatal diagnosis is available.
EPIDEMIOLOGY
• Predominant age: Life-long condition
• Predominant sex: Male = Female
Incidence
In the US: Affected individuals have been estimated at 1:20,000 live births.
RISK FACTORS
Possible familial transmission as an autosomal dominant mutation
Genetics
The pattern of occurrence is nearly always sporadic and is observed in both sexes, although there are several reported cases of familial transmission as an autosomal dominant mutation. The phenotypic expression is somewhat varied and associated with a hemizygous microdeletion of ~1.6 Mb in the 7q11.23 region which includes the elastin (ELN) and LIM-kinase (LIMK) gene.
ETIOLOGY
Microdeletion in the 7q11.23 region produced by unequal crossing over
ASSOCIATED CONDITIONS
• Developmental delay
• Growth retardation
• Cardiovascular dysfunction
• Renal dysfunction
• Attention deficit disorder (ADD)
- Frequently associated with neuropsychologic dysfunction
- Treatment for ADD is similar to methods used in the general population.


DIAGNOSIS
SIGNS AND SYMPTOMS
• The signs and symptoms observed in the classic case of Williams syndrome may be diagnostic, but the clinical presentation is somewhat varied.
• Early childhood: global developmental delay, albeit with seemingly normal speech and expressive language
- Hyperacusis
- Characteristic craniofacial features: Elfin-like facial appearance; medial eyebrow flare and stellate irises; wide mouth; long flat philtrum; upturned nose with a flat nasal bridge; dental anomalies; mild microcephaly
- Characteristic clinical features: Supravalvula aortic stenosis; peripheral pulmonary stenosis; renal artery stenosis; infantile hypercalcemia; growth retardation and short stature; slender limbs and trunk
- Characteristic cognitive/behavioral features: Weakness in abstract/visual reasoning; highly developed expressive language skills; low levels of daily living skills; age-related decreases in IQ scores
• Postpubertal males and females
- Characteristic clinical features: Hypertension; lordosis, and/or limited joint movement
- Characteristic behavioral features: Anxiety, depression, and suicidal ideation
TESTS
Lab
• Molecular-genetic (DNA) evaluation is the diagnostic test of choice and can determine the size of the deletion.
• Special tests: Affected individuals require cognitive, behavioral, psychologic, and educational evaluations to develop individual education programs.
DIFFERENTIAL DIAGNOSIS
Rule out uncomplicated hypercalcemia or supravalvular aortic stenosis.
TREATMENT
GENERAL MEASURES
• Appropriate health care: Affected individuals will generally need life-long adult supervision. Early intensive educational intervention and behavior modification should be implemented.
• Early detection will permit early intervention and intensive behavioral training.
• Treatment for hypercalcemia by controlling dietary intake of calcium and vitamin D
• Ophthalmologic evaluations are recommended for problems associated with visual acuity.
• Preventive dentistry to reduce risk of malocclusion
• Continual monitoring of cardiovascular anomalies and for hypertension
• Filtered ear protection for hyperacusis
Diet
For hypercalcemia, control intake of calcium and vitamin D.
Activity
Full activity unless cardiovascular stenoses are problematic
MEDICATION (DRUGS)
Medication for hypertension and for hyperparathyroidism
SURGERY
Treatment for aortic, pulmonary, or renal artery stenoses if needed
FOLLOW-UP
PROGNOSIS
• Individuals may need life-long supervision.
• Life span may be affected by renal dysfunction or hypertension resulting from supravalvuar stenosis and/or peripheral pulmonary stenosis
COMPLICATIONS
• Learning problems, especially in abstract/visual reasoning
• Behavioral problems concerning indifference to personal safety
• Postpubescent anxiety and depression
• Risk of cardiovascular disease and/or renal dysfunction
PATIENT MONITORING
Regular pediatric care and general health maintenance with particular attention to endocrine, renal, and cardiovascular function
REFERENCES
1. Anderson PE, Rourke BP. Williams syndrome. In: White BP, ed. Syndrome of Nonverbal Learning Disabilities. New York: Guilford Press; 1995.
2. Bayes M, Perez-Juardo LA. Williams-Beuren syndrome. In: Fisch GS, ed. Genetics and Genomics of Neurobehavioral Disorders. Totowa, NJ: Humana Press; 2003.
MISCELLANEOUS
See also: Attention Deficit/Hyperactivity Disorder; Down Syndrome; Fragile X Syndrome; Hyperparathyroidism; Hypertension, Essential; Mental Retardation