Exploring the Genetic Role of MECP2 Mutations on Phenotypic Presentation in Males: A Case Report

The purpose of this study was to explore the genotypic and phenotypic presentation of males with MECP2 -related neurodevelopmental disorders. When variants in the MECP2 gene are discovered in patients, Rett syndrome becomes a possible diagnosis. Rett syndrome, however, does not encapsulate all phenotypic variations in MECP2 gene mutations, and specific diagnosis can become tricky especially in the male population as mutations in the gene were historically thought to affect females only. The authors present a rare case of a male with a previously unpublished genetic variant resulting in a distinct clinical presentation not meeting the criteria for typical or atypical Rett syndrome.

This patient's institutional electronic medical record was accessed, and information was reviewed.

It was discovered that this patient had a maternally inherited variant in his MECP2 gene, resulting in a unique and previously undescribed form of MECP2 -related neurodevelopmental disorder, presenting with language regression followed by speech apraxia and motor discoordination.

Literature reports on various phenotypes associated with MECP2 gene mutations and elaborates on previously identified forms of typical and atypical Rett syndrome. Through this case report, the authors uncovered a pathogenic variant in MECP2 resulting in a rare phenotype of MECP2 -related neurodevelopmental disorder that has not previously been described. This should encourage clinicians to think more broadly when approaching diagnosis of children with developmental differences. This also reinforces that Rett syndrome or MECP2 mutations can often present on a spectrum, and it may be beneficial to modify diagnostic criteria to reflect this.