A 2-year-old girl presents with progressive loss of milestones after 12 months of apparently normal development, hand-wringing stereotypies replacing purposeful hand use, gait apraxia, and seizures. Genetic testing reveals MECP2 mutation on X chromosome. This syndrome occurs almost exclusively in females because:

• A MECP2 is on the X chromosome and males with mutations die in utero ✓
• B MECP2 mutations cause imprinting in females but not males
• C Males have more severe phenotype but survive with Klinefelter syndrome
• D MECP2 escapes X-inactivation and females have sufficient residual function from the normal allele

Explanation

Rett syndrome (caused by MECP2 mutations) occurs almost exclusively in females because MECP2 encodes methyl-CpG-binding protein 2, which is essential for neuronal maturation and synaptic development. Males with heterozygous (hemizygous) MECP2 mutations have only one X chromosome; without a normal MECP2 allele, the severe neurological dysfunction is typically lethal in utero or in the neonatal period. Females have two X chromosomes; X-inactivation creates a mosaic population of cells with either the normal or mutant MECP2 allele active, which is sufficient for survival. The mosaicism also explains variable severity in affected females.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.