A male infant with intellectual disability, macroorchidism, elongated face, large ears, and hyperextensible joints is found to have a CGG trinucleotide repeat expansion in the 5' UTR of the FMR1 gene (>200 repeats) with hypermethylation silencing FMR1. This trinucleotide repeat disease demonstrates which inheritance pattern?

• A Autosomal dominant with complete penetrance in all carriers
• B X-linked with genetic anticipation (repeat expansion in successive generations) ✓
• C Autosomal recessive with gonadal mosaicism
• D Mitochondrial (maternal) inheritance with heteroplasmy

Explanation

Fragile X syndrome is caused by CGG expansion on the X chromosome (FMR1 gene); full mutations (>200 repeats) cause methylation and silencing of FMRP protein, producing the syndrome predominantly in males. The repeat is unstable and expands in successive generations (anticipation), particularly when passed through a female carrier. Premutation females (55–200 repeats) carry a higher risk of expansion to full mutation in offspring.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.