A 9-year-old boy is evaluated for intellectual disability. He has a long face, large prominent ears, and a family history of two maternal uncles with intellectual disability. Testicular volume is noted to be large for age. Which genetic abnormality is most likely?

• A Mutation in the MECP2 gene on chromosome Xq28
• B Deletion of the paternal copy of 15q11-q13
• C Trinucleotide CAG repeat expansion in the androgen receptor gene
• D Expansion of CGG trinucleotide repeats in the FMR1 gene ✓

Explanation

Fragile X syndrome is the most common inherited cause of intellectual disability in boys. It results from CGG trinucleotide expansion in the FMR1 gene with associated CpG methylation and transcriptional silencing. Large ears, long face, and postpubertal macroorchidism are characteristic, and transmission through carrier mothers explains affected maternal uncles. Paternal 15q11 deletion causes Prader-Willi syndrome, MECP2 mutation causes Rett syndrome, and CAG expansion in the androgen receptor causes Kennedy disease.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.