A child had severe hypotonia and feeding difficulty requiring nasogastric tube in the neonatal period. By 3 years he has developed hyperphagia, marked obesity, small hands and feet, almond-shaped eyes, and bilateral undescended testes. Which genetic mechanism most commonly underlies this condition?

• A Deletion of the maternally inherited 15q11-q13 region
• B Deletion of the paternally inherited 15q11-q13 region ✓
• C Paternal uniparental disomy of chromosome 15
• D Expansion of a trinucleotide repeat on chromosome 4

Explanation

Prader-Willi syndrome arises from loss of expression of paternally inherited genes in the imprinted 15q11-q13 region; a paternal deletion accounts for roughly 70 percent of cases. Deletion of the same region when maternally inherited causes Angelman syndrome, characterized by severe intellectual disability, ataxia, laughter, and seizures rather than hyperphagia and obesity. Maternal uniparental disomy of chromosome 15 also causes Prader-Willi syndrome but is less common than the paternal deletion.

Reference: Nelson Textbook of Pediatrics, 22nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.