A 3-year-old boy is referred for global developmental delay, absent speech, happy demeanor with frequent unprovoked laughter, seizures (particularly myoclonic), and ataxic gait. EEG shows large amplitude spike-wave discharges. Which genetic mechanism is responsible for THIS specific syndrome?
- A Deletion of maternal chromosome 15q11.2–q13 ✓
- B Deletion of paternal chromosome 15q11.2–q13
- C Trinucleotide CAG repeat expansion
- D Uniparental disomy of chromosome 15 (paternal)
Explanation
Angelman syndrome is caused by loss of function of the UBE3A gene on the MATERNAL chromosome 15q11-q13. The classic presentation includes severe intellectual disability, absent speech (but appears happy), ataxic gait, seizures (especially myoclonic/absence), and characteristic EEG with high-amplitude spike-and-wave activity. The deletion on the maternal chromosome 15q11-q13 accounts for ~70% of cases; paternal UPD (father provides both chromosome 15s), imprinting defects, or UBE3A mutations account for the rest. Prader-Willi syndrome, by contrast, is caused by loss of the PATERNAL contribution to 15q11-q13. CAG repeat expansion causes Huntington's disease.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.