A 10-year-old boy has a head circumference of 47 cm (expected >52 cm for age). He has mild intellectual disability, marked obesity with predominantly truncal fat, hypogonadism (small testes, undescended), and a history of neonatal hypotonia and poor feeding. Which genetic mechanism is implicated?

• A Deletion of chromosome 15q11-q13 of maternal origin (Angelman syndrome)
• B Deletion of chromosome 17p11.2 (Smith-Magenis syndrome)
• C Paternal deletion of chromosome 15q11-q13 (Prader-Willi syndrome) ✓
• D Trisomy 21 with hypothyroidism causing obesity

Explanation

Prader-Willi syndrome (PWS) is caused by absent expression of the paternal copy of 15q11-q13 (imprinted region). This occurs by: paternal deletion (70%), maternal uniparental disomy (25%), or imprinting centre defects. Classic features: neonatal hypotonia and poor feeding (phase 1), followed by hyperphagia and obesity (phase 2) around age 2–4, hypogonadism, short stature, intellectual disability, and small hands/feet. Angelman syndrome is the maternal deletion counterpart, presenting with severe intellectual disability, seizures, happy affect, and absent speech — NOT obesity.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.