MECP2 Variants in Males: More Common than Previously Appreciated

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• MECP2 variants are a rare cause of neurological disorders in males.
• Rett syndrome is typically associated with females, but males can be affected by MECP2 mutations.

Purpose of the Study:

• To characterize the age and MECP2 variant spectrum in recently identified males.
• To lay the groundwork for future studies on the clinical presentation of males with MECP2 variants.

Main Methods:

• Genetic data for MECP2 variants were obtained from the Parent Group for Males.
• Information on variant inheritance (de novo or maternal) and mosaicism was collected.

Main Results:

• Fifty-nine males with MECP2 variants were identified, aged 2-28 years (median 7.0, mean 10.8).
• Most variants were de novo (78.0%); 18.6% of males had mosaicism.
• The total cohort, including prior studies, comprised 85 males, with 27 deceased.

Conclusions:

• Characterizing males with MECP2 variants is crucial for improving diagnosis, care, and research.
• These findings support the development of targeted therapies, emphasizing equitable access for males.