A 5-year-old boy presents with developmental delay, long face, large ears, prominent jaw, and macroorchidism noted on examination. Family history shows affected males in successive generations with transmission from unaffected carrier mothers. What is the underlying genetic abnormality?

• A Expansion of CGG trinucleotide repeat in the FMR1 gene ✓
• B Deletion of the elastin gene on chromosome 7
• C Deletion of TBX1 on chromosome 22q11.2
• D Mutation of the MECP2 gene on the X chromosome

Explanation

Fragile X syndrome results from expansion of a CGG trinucleotide repeat (>200 full mutation) in the FMR1 gene at Xq27.3 with methylation-induced silencing. It is the commonest inherited cause of intellectual disability after Down syndrome. Macroorchidism after puberty is characteristic. MECP2 mutation causes Rett syndrome in girls, and elastin deletion causes Williams syndrome, both clinically distinct here.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.