What causes MEF2C Related Syndrome?

MEF2C Related Syndrome presents itself when there are pathogenic changes to the MEF2C gene. These changes can prevent the gene from working as it should.

The MEF2C gene encodes for a transcription factor and is known to regulate the expression of nearly 2000 genes important to the development and maintenance of many tissues within the body, including the brain. Neuron growth, synaptic development, maintenance, and remodeling are just a few of the processes involving MEF2C that are critical for proper nervous system development and function.

MEF2C dysfunction been closely linked to Autism, Schizophrenia, ALS, Intellectual Disability, Cerebral Palsy and Epilepsy; and genetic variation in MEF2C and its direct target genes within cortical neurons contribute to variance in cognition within the general population.

We are finding that there are different types of MEF2C pathogenic variants out there. It is our goal to fund research and development that will lead to treatments and a cure for all MEF2C variants.

Types of Genetic Variants

Copy Number Variants

A copy number variant means a person has a large amount of extra (duplication) or missing (deletion) genetic material. A copy number variant is named by its chromosome location. As an example, 5q14.3 deletion describes a deletion on chromosome 5 that includes the MEF2C gene. 

Single Nucleotide Variants

A single nucleotide variant means a spelling change is found within a gene. A person has all the typical genes, but there is a change in the way a gene is spelled.  

• Missense Variant - A single letter change in DNA causes one building block to change (i.e. MEF2C c.113T>C)

• Nonsense Variant - A single letter change in the DNA causes the protein to be shorter than typical (i.e. MEF2C c.860C>A)

• Insertions & Duplications - Insertions and duplications can add a nucleotide to the DNA sequence

• Deletion - A deletion can remove a nucleotide from the DNA sequence

• Frameshift Variant - An insertion or deletion that changes the gene’s reading frame

The MEF2C Natural History Study with the lab of Dr. Wendy Chung, Chief of the Department of Pediatrics, Boston Children’s Hospital & Mary Ellen Avery Professor at Harvard Medical School, will include different types of known variants within our patient group.

How rare is this diagnosis?

At this time we have a population of approximately 400 patients globally, with nearly half of our patients in the United States. We strongly suspect that there are many more patients out there, not yet diagnosed. If patients do not have seizures, they are often diagnosed with autism / cognitive and processing disabilities, and many are not advised to have genetic tests performed to determine if there is an underlying genetic condition causing these symptoms.

What are the symptoms?

MEF2C related syndrome presents a broad range of symptoms including:

• Global Developmental Delay

• Severely Impaired or Absent Language

• Profound Learning Difficulties

• Epilepsy (seizures)

• Severe Hypotonia / can be mixed with hypertonia

• Stereotypical & Repetitive Movements

• Self stimulatory behavior

• Hyperactivity

• Sleeping Difficulties

• Feeding Difficulties

MEF2C related syndrome is considered a severe form of Autism Spectrum Disorder (ASD).

Is there a treatment?

There are no MEF2C targeted therapeutics currently available; and therefore we must invest in extensive research and development to find treatments and a cure. 

Learn more about this critical research and the ongoing path to therapy development for patients with MEF2C related syndrome.