A 7-year-old boy has intellectual disability, a long face with large ears and a prominent jaw, hyperextensible joints, and post-pubertal macroorchidism. His maternal uncle and a male cousin have intellectual disability. Which single test will confirm the diagnosis?

• A Karyotype with high-resolution banding
• B Serum testosterone and LH levels
• C Urinary metabolic screening for mucopolysaccharides
• D FMR1 gene analysis for CGG trinucleotide repeat expansion ✓

Explanation

Fragile X syndrome, the commonest inherited cause of intellectual disability in boys, results from CGG repeat expansion (>200 repeats, full mutation) with methylation silencing of the FMR1 gene at Xq27.3. It shows X-linked inheritance with transmission through carrier mothers, explaining affected maternal male relatives. Karyotype can show the fragile site but lacks sensitivity and specificity compared with molecular testing. Macroorchidism reflects testicular enlargement, not hormonal excess.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.