A 6-month-old male infant has large testes, prominent ears, a long narrow face, and macrocephaly. His mother mentions that his maternal uncle was intellectually disabled and had similar facial features. CGG repeat analysis reveals 230 repeats in the FMR1 gene. Which statement best describes the inheritance pattern?

• A Autosomal dominant with incomplete penetrance
• B X-linked recessive with trinucleotide repeat expansion (anticipation) ✓
• C X-linked dominant with lethality in hemizygous males
• D Mitochondrial inheritance with maternal transmission

Explanation

Fragile X syndrome is the most common inherited cause of intellectual disability, caused by CGG trinucleotide repeat expansion in the FMR1 gene on the X chromosome. Normal individuals have <55 repeats; premutation carriers have 55–200 repeats; full mutation (>200 repeats) causes gene silencing. It follows X-linked inheritance with anticipation (repeats expand with successive generations, especially through maternal transmission). Affected males (hemizygous) have full expression; carrier females (heterozygous) may have partial phenotype due to random X-inactivation.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.