Prevalence and spectrum of MECP2 variants in patients clinically diagnosed with cerebral palsy

Cerebral palsy (CP) is the most common motor impairment in children, with genetic factors increasingly demonstrated in its pathogenesis. Variants in MECP2 , a crucial transcriptional regulator in neuronal development, have been recurrently implicated in multiple independent CP studies. However, the prevalence and spectrum of MECP2 variants in CP remains incompletely evaluated. Here, we conducted a retrospective analysis on a CP cohort comprising 1,578 unrelated Chinese patients to assess the presence of MECP2 variants. We identified a case series of 11 CP patients with MECP2 variant in our cohort, including 6 loss-of-function variants and 5 MECP2 duplication variants, accounting for 0.70% of 1,578 CP cases. Systematic review and meta-analysis on the genetic studies of CP reveal that the overall MECP2 -related molecular diagnostic yield is 0.68% (95% CI, 0.43%-0.99%). Our study highlights the prevalence of MECP2 variants in CP and broadens the scope of MECP2 -related diseases, thereby offering guidance for diagnosis, prognosis, family counseling, clinical surveillance, and future therapeutic strategies for related patients.