MECP2 -Related Disorders in Males

Methyl CpG binding protein 2 ( ) is located at Xq28 and is a multifunctional gene with ubiquitous expression. Loss-of-function mutations in are associated with Rett syndrome (RTT), which is a well-characterized disorder that affects mainly females. In boys, however, mutations in can generate a wide spectrum of clinical presentations that range from mild intellectual impairment to severe neonatal encephalopathy and premature death. Thus, males can be more difficult to classify and diagnose than classical RTT females. In addition, there are some variants of unknown significance in , which further complicate the diagnosis of these children. Conversely, the entire duplication of the gene is related to duplication syndrome (MDS). Unlike in RTT, in MDS, males are predominantly affected. Usually, the duplication is inherited from an apparently asymptomatic carrier mother. Both syndromes share some characteristics, but also differ in some aspects regarding the clinical picture and evolution. In the following review, we present a thorough description of the different types of variants and alterations that can be found in males, and explore several genotype-phenotype correlations, although there is still a lot to understand.