Review Question - QID 108377

In this previously normal female patient with progressive cognitive and motor decline, the most likely diagnosis is Rett syndrome.

Rett syndrome is an X-linked dominant genetic disorder marked by normal development until the age of 4 with progressive verbal and motor decline. In males, the genetic defect is incompatible with life. Stereotypic behavior such as hand-wringing is often seen (Illustration A). The disease can inherited from an unaffected mother as a result of X-inactivation, or as a de novo mutation.

Illustration A is a clinical photo of a patient with Rett syndrome. Note the stereotypic hand-wringing behavior.

Incorrect Answers:
Answer 1: Angelman syndrome is a genetic disease caused by disruption of the maternally expressed UBE3A allele combined with a paternally imprinted (turned off) chromosome 15. Symptoms include severe cognitive disability, frequent seizures, ataxia, speech impairment, hyperactivity, and inappropriate laughter.

Answer 3: Beckwith–Wiedemann syndrome is an autosomal dominant disorder caused by a deletion on chromosome 11 marked by Wilms' tumors, hemihypertrophy of body, and organomegaly.

Answer 4: Prader-Willi syndrome is a genetic disease caused by disruption of the paternally expressed UBE3A allele combined with a maternally imprinted (turned off) chromosome 15. Symptoms include mental retardation, hyperphagia, hypogonadism, neonatal hypotonia, and behavior problems.

Answer 5: McCune-Albright syndrome is an post-zygotic genetic disorder defined by the presence of café au lait spots, fibrous dysplasia, multiple endocrine abnormalities including precocious puberty, and renal phosphate wasting.