A male infant with macroglossia, umbilical hernia, hypoglycemia, and hemihypertrophy is diagnosed with Beckwith-Wiedemann syndrome. This overgrowth disorder primarily results from dysregulation of imprinting at which chromosomal locus?

• A 15q11-q13 — affecting SNRPN and UBE3A imprinting
• B 7q11.23 — affecting LIMK1 and ELN deletion
• C 22q11.2 — affecting TBX1 and DGCR8
• D 11p15.5 — affecting IGF2 and H19 imprinting ✓

Explanation

Beckwith-Wiedemann syndrome results from imprinting dysregulation at chromosome 11p15.5, where the IGF2 (insulin-like growth factor 2, normally expressed from the paternal allele) and H19 (expressed from the maternal allele) genes are reciprocally imprinted. Mechanisms include paternal uniparental disomy, loss of imprinting at IGF2, or CDKN1C (p57KIP2) mutations; the net result is biallelic IGF2 expression causing somatic overgrowth and predisposition to Wilms tumor and hepatoblastoma. Chromosome 15q11-q13 imprinting involves Prader-Willi/Angelman syndromes.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.