A 2-year-old boy has macrocephaly, macro-orchidism, prominent ears, mild-to-moderate intellectual disability, and a history of otitis media. His maternal grandfather had mild cognitive impairment and tremor. The most likely diagnosis and inheritance pattern is:

• A Klinefelter syndrome (47,XXY) — X-linked recessive
• B Sotos syndrome — NSD1 mutation, autosomal dominant
• C Fragile X syndrome — X-linked inheritance with FMR1 CGG trinucleotide repeat expansion; shows anticipation (premutation carriers can develop FXTAS) ✓
• D Angelman syndrome — maternal deletion 15q11-q13

Explanation

Fragile X syndrome is the most common inherited cause of intellectual disability in males. Key features include macro-orchidism (post-pubertal), large ears, prominent jaw, macrocephaly, and behavioral features (hyperactivity, autism spectrum features). It is caused by CGG triplet expansion in FMR1 gene on X chromosome (>200 repeats = full mutation). The maternal grandfather's tremor and ataxia suggest Fragile X Tremor Ataxia Syndrome (FXTAS) seen in premutation carrier males (55–200 repeats). The anticipation pattern is characteristic.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.