A previously healthy 14-month-old girl stops acquiring milestones. Over months she loses purposeful hand use and speech, develops stereotyped midline hand-wringing movements, breath-holding spells with hyperventilation, and her head circumference percentile falls progressively. She remains socially engaged with eye contact. Which inheritance pattern applies?
- A X-linked dominant, lethal in most males ✓
- B Autosomal recessive
- C Mitochondrial maternal transmission
- D Autosomal dominant with paternal imprinting
Correct answer: A. X-linked dominant, lethal in most males
Explanation
Rett syndrome results from mutations in MECP2, an X-linked dominant gene; affected boys are usually lost early, so almost all patients are girls. The hallmark is normal development for 6 to 18 months followed by regression with loss of purposeful hand skills, stereotypic hand wringing, acquired microcephaly from decelerating head growth, and seizures. Social engagement and eye contact are characteristically preserved, which helps separate Rett from autism. Autosomal recessive inheritance does not fit.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.