Header

UZH-Logo

Maintenance Infos

The MEF2C-related and 5q14.3q15 microdeletion syndrome


Zweier, M; Rauch, A (2012). The MEF2C-related and 5q14.3q15 microdeletion syndrome. Molecular Syndromology, 2(3-5):164-170.

Abstract

Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target.

Abstract

Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target.

Statistics

Citations

Altmetrics

Downloads

4 downloads since deposited on 29 Jan 2013
3 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:29 Jan 2013 12:33
Last Modified:07 Dec 2017 19:08
Publisher:Karger
ISSN:1661-8769
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000337496
PubMed ID:22670137

Download

Download PDF  'The MEF2C-related and 5q14.3q15 microdeletion syndrome'.
Preview
Content: Published Version
Filetype: PDF
Size: 401kB
View at publisher