Genotypes and Phenotypes of MEF2C Haploinsufficiency Syndrome: New Cases and Novel Point Mutations
Open Access
- 13 May 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Pediatrics
Abstract
Aim: MEF2C haploinsufficiency syndrome (MCHS) is a severe neurodevelopmental disorder. We describe the clinical phenotypes and genotypes of seven patients with MCHS to enhance the understanding of clinical manifestations and genetic alterations associated with MCHS. Method: Seven patients (6 females and 1 male, aged between 2 years 5 months and 6 years) who had MEF2C mutations, and their parents underwent trio-based whole-exome sequencing; subsequently, their clinical features were assessed. A literature review of patients with MCHS was performed by searching the PubMed and Online Mendelian Inheritance in Man databases. Results: Seven mutations were identified, of which six were unreported in the past; of the reported cases, five patients had de novo mutations but two had an undefined inheritance pattern. All patients presented delays in developmental milestones, severe intellectual disabilities and lack of speech. Six patients exhibited infantile hypotonia, five patients experienced stereotypic movements and were unable to walk, four patients exhibited poor eye contact indicative of autism and two showed poor performance. While six patients experienced seizure, five among them became seizure free after receiving anti-seizure medicine. Three patients showed a regression in their development, whereas the mothers of two patients exhibited mosaicism but were healthy without any abovementioned symptoms. Interpretation: Regression was not a common phenomenon but occurred in MCHS. The prognosis of MCHS patients with epilepsy was good, but most patients can achieve a seizure-free status. Healthy people may have low-level mosaicism and carry a pathogenic MEF2C mutation.This publication has 17 references indexed in Scilit:
- PartialMEF2Cdeletion in a Cypriot patient with severe intellectual disability and a jugular fossa malformation: Review of the literatureAmerican Journal of Medical Genetics Part A, 2015
- Clinical whole exome sequencing in child neurology practiceAnnals of Neurology, 2014
- MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathwaysneurogenetics, 2013
- Refining the phenotype associated with MEF2C point mutationsneurogenetics, 2012
- Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expressionHuman Mutation, 2010
- Refining the phenotype associated with MEF2C haploinsufficiencyClinical Genetics, 2010
- MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformationsJournal of Medical Genetics, 2009
- MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and functionProceedings of the National Academy of Sciences of the United States of America, 2008
- Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem CellsJournal of Neuroscience, 2008
- A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic DifferentiationScience, 2006