Clinical Guidance

At least two individuals with a deletion encompassing only MEF2C exons 1-3 presented with cutaneous vascular malformations, suggesting a possible genotype-phenotype correlation . Individuals with pathogenic variants affecting the proximal region of the MEF2C protein (e.g., within the MADS or MEF2 domains) may be more severely affected than individuals with more distal pathogenic variants . Possible genotype-phenotype correlations associated with MEF2C (e.g., variant type or variant position) require further study. Note: Several reported MEF2C genotype-phenotype correlations compare MEF2C single-nucleotide variants to larger contiguous deletions that encompass additional genes; these are not included in this GeneReview.

Source: GeneReviews — "MEF2C-Related Disorder"

Penetrance

Penetrance is 100%; all individuals who have a MEF2C pathogenic variant have clinical manifestations of the disorder. There have been no reports of unaffected individuals with a pathogenic variant in MEF2C.

Source: GeneReviews — "MEF2C-Related Disorder"

Diagnostic Criteria

Suggestive Findings

MEF2C-related disorder should be considered in probands with the following clinical and brain MRI findings and family history.

Clinical findings

Source: GeneReviews — "MEF2C-Related Disorder"

Differential Diagnosis

The phenotypic features associated with MEF2C-related disorder are not sufficient to diagnose this condition clinically; all disorders with intellectual disability and seizures without other distinctive findings should be considered in the differential diagnosis. See OMIM Phenotypic Series for genes associated with:

• Autosomal dominant intellectual developmental disorders

• Autosomal recessive intellectual developmental disorders

• Nonsyndromic X-linked intellectual developmental disorders

• Syndromic X-linked intellectual developmental disorders

Classic Rett syndrome and Angelman syndrome can be considered in individuals presenting with stereotypic hand movements, intellectual disability, and seizures .

Table 3.

Genes of Interest in the Differential Diagnosis of MEF2C-Related Disorder

Source: GeneReviews — "MEF2C-Related Disorder"

Management Guidelines

No clinical practice guidelines for MEF2C-related disorder have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MEF2C-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

MEF2C-Related Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To incl assessment of:

• Gross motor fine motor skills

• Mobility, ADL, need for adaptive devices

• Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

Neurologic

| • Neurologic eval

• Cognitive assessment

| • To incl brain MRI

• Consider EEG if seizures are a concern.

Gastrointestinal/

Feeding

| Gastroenterology/ nutrition/ feeding team eval | • To incl eval of aspiration risk nutritional status

• Assess for GERD constipation.

• Consider eval for gastrostomy tube placement in persons w/dysphagia /or aspiration risk.

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for ASD, hyperkinesis, agitation, self-injury, breathing issues, sl...

Source: GeneReviews — "MEF2C-Related Disorder"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "MEF2C-Related Disorder"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. MEF2C-Related Disorder: Recommended Surveillance

Source: GeneReviews — "MEF2C-Related Disorder"