A 3-year-old girl has a history of microcephaly, severe intellectual disability, happy demeanor with inappropriate laughter, absence/atonic seizures, and absent speech. EEG shows characteristic high-amplitude slow spikes. The genetic mechanism is:
- A Paternal deletion of chromosome 15q11-q13 (maternal imprinting) or maternal UPD 15
- B Maternal deletion of chromosome 15q11-q13 (paternal imprinting) or paternal UPD 15 or UBE3A mutation ✓
- C Trinucleotide repeat expansion in FMR1 gene
- D Trisomy 21 with chromosome 15 involvement
Correct answer: B. Maternal deletion of chromosome 15q11-q13 (paternal imprinting) or paternal UPD 15 or UBE3A mutation
Explanation
This is Angelman syndrome, caused by loss of function of the maternally expressed UBE3A gene on chromosome 15q11-q13. The mechanisms include: maternal deletion (70%), paternal uniparental disomy (UPD) 15 (2–3%), imprinting center defects, or UBE3A point mutations. The opposite genetic mechanism (paternal deletion/maternal UPD 15) causes Prader-Willi syndrome. This distinction — same chromosomal region, opposite parent of origin, opposite clinical phenotype — is a classic genetics question.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.