History of Genetics in Rett Syndrome
- Early Theories:
- X-linked dominant, male-lethal (XDML) inheritance model.
- Differences in severity linked to X-chromosome inactivation (XCI).
- Key Genetic Discoveries:
- MECP2 mutations identified as the usual cause of classic RTT.
- Mutations arise predominantly during spermatogenesis.
- Rare Cases:
- Male presentations: Mosaicism or Klinefelter syndrome (47,XXY).