Zweier M, Rauch A
Institute of Human Genetics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Mol Syndromol. 2012 Apr;2(3-5):164-170. doi: 10.1159/000337496. Epub 2012 Apr 16.
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.
与位于5q14.3的常染色体转录因子MEF2C相关的疾病于2009年首次被描述，此后已演变成较为常见的微缺失综合征之一。在一个更大的队列中进行的突变筛查显示，在约1%的中度至重度智力残疾患者中存在MEF2C的杂合性新生突变，并且基因内缺失和多基因微缺失患者的表型相似。临床上，MEF2C相关疾病的特征为严重智力残疾、无言语能力和有限的行走能力、肌张力减退、癫痫发作以及各种轻微脑异常。大多数患者表现出相似的面部特征，包括宽额头、扁平鼻梁、肌张力减退的嘴巴和小下巴，以及斜视，但这种表型在临床上尚未得到充分认识。疾病进程通常相当一致，但点突变和较小缺失的患者似乎有更高的获得行走技能的机会和更低的难治性癫痫发作风险。微缺失还包括RASA1基因的患者表现出各自的毛细血管和动静脉畸形及瘘管综合征的特征。与雷特综合征的表型重叠是由一条共同途径解释的，因此，在MEF2C缺陷患者中可测量到MECP2和CDKL5表达降低。因此，对该途径的进一步研究最终可能会导致一个共同的治疗靶点。
