MECP2-Related Disorders in Males

Abstract

Methyl CpG binding protein 2 (MECP2) is located at Xq28 and is a multifunctional gene with ubiquitous expression. Loss-of-function mutations in MECP2 are associated with Rett syndrome (RTT), which is a well-characterized disorder that affects mainly females. In boys, however, mutations in MECP2 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 MECP2, which further complicate the diagnosis of these children. Conversely, the entire duplication of the MECP2 gene is related to MECP2 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 MECP2 variants and alterations that can be found in males, and explore several genotype-phenotype correlations, although there is still a lot to understand.

Keywords: MECP2; MECP2 duplication syndrome; Rett syndrome; encephalopathy; loss-of-function; males; point mutation.

Figure 1

Frequency of each sex among patients harbouring mutations in MECP2 and those with a duplication of the entire MECP2. Sources of information are RettBASE for mutations in MECP2 and 82 articles from PubMed containing the term “MECP2 duplication” for the patients with the duplication.