A 5-year-old child passed all developmental milestones appropriately until age 18 months, then began losing acquired speech, hand purposeful use, and social skills. She now has stereotyped hand-wringing movements, irregular breathing, and acquired microcephaly. Which gene mutation is responsible for this syndrome?

• A FMR1 (Xq27.3)
• B TSC2 (16p13.3)
• C SHANK3 (22q13.3)
• D MECP2 (Xq28) ✓

Explanation

Rett syndrome is caused by mutations in MECP2 (methyl-CpG binding protein 2) on chromosome Xq28. It almost exclusively affects girls (hemizygous boys are usually lethally affected). The classic presentation includes normal early development followed by regression between 6–18 months, with loss of purposeful hand use, acquired stereotyped hand-wringing, breathing irregularities, seizures, and acquired microcephaly. It is the second most common genetic cause of intellectual disability in females after Down syndrome. FMR1 causes Fragile X, SHANK3 mutations cause Phelan-McDermid syndrome (22q13 deletion).

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.