Comparative analysis of clinical phenotypes and genetic characteristics in MEF2C-associated neurodevelopmental disorders.

BACKGROUND

Myocyte enhancer factor 2C (MEF2C) is among the important genes associated with neurodevelopmental disorders (NDDs). The phenotypic distinctions between MEF2C pathogenic variants and 5q14.3 microdeletions remain unclear.

METHODS

We retrospectively collected the information of patients from our centre between May 2019 and October 2024 and identified them as having MEF2C mutations by whole-exome sequencing (WES). We searched the literature related to MEF2C mutations and 5q14.3 microdeletions and summarized the clinical features and genetic characteristics of the patients.

RESULTS

Five patients with MEF2C mutations were identified from our hospital, and 34 articles were selected for analysis. Data from 62 MEF2C-associated copy number variations (CNVs) and 42 MEF2C mutations were analysed. We found that regression was more common in the mutation group (21.6 %, 8/37) than in the CNV group (2.0 %, 1/51; P = 0.008). Patients with mutations in MEF2C were more likely to present with a history of febrile seizures (45.2 % vs. 25.8 %, P = 0.040) and autistic traits (91.9 % vs. 74.5 %, P = 0.037). Myoclonic seizures (29.4 % vs. 70.6 %, P = 0.025), infantile epileptic spasm syndrome (3.3 % vs. 31.8 %, P = 0.018), refractory epilepsy (11.1 % vs. 47.8 %, P = 0.012), diffuse epileptiform discharges from electroencephalograms (15.0 % vs. 42.9 %, P = 0.2) and abnormal corpus callosum (23.1 % vs. 55.9, P = 0.06) may occur more often in the CNV group.

CONCLUSION

Patients with CNVs presented a higher prevalence of refractory epilepsy and vascular malformations, whereas those with point mutations more frequently presented with developmental regression, febrile seizure history and autistic traits. These genotype-phenotype correlations could inform genetic testing strategies.