A 5-year-old girl with normal development till 18 months now presents with hand-wringing stereotypies, loss of purposeful hand use, autistic features, and decelerating head growth. EEG shows characteristic multifocal spike-wave pattern. The most likely diagnosis and causative gene mutation is:
- A Angelman syndrome; UBE3A mutation on maternal chromosome 15
- B Childhood disintegrative disorder; SHANK3 mutation
- C Rett syndrome; MECP2 mutation on X chromosome ✓
- D Landau-Kleffner syndrome; acquired epileptic aphasia
Explanation
Rett syndrome is caused by mutations in MECP2 (methyl-CpG binding protein 2) on Xq28, almost exclusively in females (hemizygous males die in utero or have severe neonatal encephalopathy). The classic regression phase (18 months to 3 years) features loss of purposeful hand use replaced by stereotypic hand-wringing, autistic regression, and decelerating head circumference. EEG shows multifocal spike-wave activity. Angelman syndrome has prominent seizures but different features (happy demeanor, absence of hand-wringing). Landau-Kleffner is an epileptic aphasia syndrome without hand-wringing.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.