MEF2Crelated

MEF2C-related refers to a group of neurodevelopmental conditions caused by disruption of the MEF2C gene, which encodes myocyte enhancer factor 2C, a transcription factor of the MEF2 family. MEF2C regulates activity-dependent gene expression in neurons and participates in synaptic development and plasticity. It also has roles in muscle differentiation and heart development, illustrating its broad patterning functions. In the nervous system, MEF2C influences neuronal maturation, dendritic spine formation, and the balance of excitatory and inhibitory signaling.

Most MEF2C-related cases arise from haploinsufficiency of MEF2C due to microdeletions involving the gene or pathogenic variants within MEF2C. In many instances, the causative change is de novo. The clinical presentation is variable but typically includes neurodevelopmental delay, intellectual disability, impaired or absent speech, and hypotonia; seizures are common in a substantial subset. Some individuals show autistic features, behavioral differences, and mild dysmorphic traits; brain imaging may reveal non-specific findings.

Diagnosis is achieved through genetic testing, including chromosomal microarray to detect deletions and sequencing to identify point mutations or small indels. Management is multidisciplinary and supportive, emphasizing early intervention, speech and language therapy, physical therapy, and epilepsy management where appropriate. While there is no cure, understanding MEF2C’s regulatory networks is informing research into targeted therapies and potential precision approaches in the longer term.

See also: MEF2 family, neurodevelopmental disorders, haploinsufficiency.