A 5-year-old boy has global developmental delay, a long face, large prominent ears, macrocephaly, joint laxity, and attention deficit. His maternal uncle also has intellectual disability. Which investigation will establish the diagnosis?
- A FMR1 CGG repeat expansion analysis by methylation-sensitive PCR ✓
- B MECP2 gene sequencing
- C Standard G-banded karyotype
- D SMN1 gene deletion testing
Correct answer: A. FMR1 CGG repeat expansion analysis by methylation-sensitive PCR
Explanation
Fragile X syndrome, the commonest inherited cause of intellectual disability in boys, results from CGG trinucleotide expansion (>200 repeats, full mutation) with methylation of the FMR1 promoter on Xq27.3, detected by methylation-sensitive PCR. It shows X-linked dominant inheritance with transmission through carrier mothers, explaining the affected maternal uncle. Standard karyotyping misses the fragile site in most cases, MECP2 causes Rett syndrome, and SMN1 deletion causes spinal muscular atrophy.
Reference: Nelson Textbook of Pediatrics, 22nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.