Pathogenic variants in the MEF2C gene cause a neurodevelopmental disorder called ‘Mental Retardation, Autosomal Dominant 20’ or ‘Chromosome 5q14.3 Deletion Syndrome’ (MIM#613443).

The MEF2C gene (MIM*600662), located on chromosome 5, belongs to the myocyte enhancer factor-2 (MEF2) family of transcription factors.

Engels et al. first described in 2009, three patients with a chromosome 5q14.3 microdeletion including MEF2C. Then, in 2010, Le Meur et al. showed that MEF2C haploinsufficiency caused by chromosome 5q14.3 microdeletion or point mutation is responsible for the same clinical presentation. They also reported one patient with chromosome 5q14.3 duplication.

Main clinical features

The clinical presentation is characterised by severe global developmental delay with absence of speech, limited ambulation, hypotonia, seizures and stereotypic movements.

Phenotypic overlap with Rett and Angelman syndromes has been noted. In contrast to patients with Rett syndrome, period of developmental regression or microcephaly are rarely reported.

Subtle facial signs, ‘ceiling-gazing’ behaviour and the presence of hemangiomas could be a clue to a MEF2C haploinsufficiency clinical diagnosis.

Regarding the symptoms of patients with MEF2C duplication, only 5 patients have been reported so far. More patient data is needed to examine the clinical presentation of these patients.


The disorder is caused by heterozygous pathogenic variants, which usually occur de novo. In principle, autosomal dominant inheritance is possible and each person with a MEF2C pathogenic variant has a 50% chance that any child they have will inherit that variant. To our best knowldege, all the affected people are the first person in their family to have the pathogenic variant in the MEF2C gene and there have been no reports of germ cell mosaicism.


The exact prevalence is unknown. Pathogenic variants in the MEF2C gene are rare. Only 60 individuals with pathogenic variants in the MEF2C gene (11 point mutations, 44 microdeletions and 5 duplications) have been reported in the literature, so far.