A 4-year-old girl has severe intellectual disability, bursts of inappropriate laughter, ataxic jerky gait, microcephaly, and refractory seizures. She had normal birth history. Her brother is unaffected. Which mechanism most commonly underlies this disorder?

• A Loss of paternally expressed genes at 15q11-q13
• B Loss of maternally expressed UBE3A in the brain due to maternal deletion of 15q11-q13 ✓
• C Uniparental disomy resulting in two paternal copies of chromosome 15
• D Expansion of GAA repeats in the frataxin gene

Explanation

Angelman syndrome features severe intellectual disability, happy demeanor with paroxysmal laughter, ataxia, seizures, and microcephaly. It arises from loss of function of the maternally expressed UBE3B gene, which is imprinted such that only the maternal allele is active in the brain. About 70 percent of cases result from maternal deletion of 15q11-q13. Loss of paternal 15q11-q13 genes produces Prader-Willi instead, and GAA expansion in frataxin causes Friedreich ataxia.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.