MECP2 Mutation: myoclonic epilepsy and Rett syndrome features in a rare missense variant

<h3>Background</h3> Rett syndrome, an X-linked dominant neurodevelopmental disorder primarily affecting females, is characterised by developmental regression after initial normal development, predominantly resulting from de novo mutations in the MECP2 gene. We report a rare missense MECP2 mutation p.(Arg309Trp), presenting with myoclonic epilepsy and only two features of Rett syndrome. <h3>Case Report</h3> A 17-year-old woman presented with myoclonic epilepsy on a background of mild intellectual disability subtle dysmorphism and kyphoscoliosis. Milestones, particularly speech, were slightly delayed. She had an explosive onset of seizures at the age of 17 with varied semiology, predominantly myoclonic. Brain MRI was normal. Trio-exome sequencing identified a de novo MECP2 missense mutation (NM_004992.3:c.925C&gt;T p.(Arg309Trp)). Contrary to the comprehensive Rett syndrome diagnostic criteria, our patient fulfilled only one major and one supporting criterion. Currently, she is managed on a regimen of three antiseizure medications, with improved seizure control. The five other patients described with this mutation also had intellectual disability and mild dysmorphism. None had Rett syndrome and only three had epilepsy.¹ <h3>Conclusion</h3> This case highlights and expands the spectrum of MECP2 mutations, emphasizing these missense mutations as potential contributors to epilepsy in patients with very few features of Rett syndrome. <h3>Reference</h3> Schönewolf-Greulich B, <i>et al.</i> ‘The MECP2 variant c.925C&gt;T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.’ <i>Clinical Genetics</i> 2016;<b>89</b>(6):733–8. doi:10.1111/cge.12769.