GENE GUIDE

MEF2C-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has MEF2C-Related Syndrome.
a doctor sees a patient

MEF2C-related syndrome is also called MEF2C Haploinsufficiency Syndrome (MCHS). For this webpage, we will be using the name MEF2C-related syndrome to encompass the wide range of variants observed in the people identified

MEF2C-related syndrome happens when there are changes to the MEF2C gene. These changes can keep the gene from working as it should.

Key Role

The MEF2C gene is important for muscle and brain cells.

Symptoms

Because the MEF2C gene is important in the development and function of brain cells, many people who have MEF2C-related syndrome have:

  • Intellectual disability and/or developmental delay
  • Speech difficulties or no speech
  • Low muscle tone
  • Autism or features of autism
  • Seizures
  • Heart issues
  • Small head size
  • Gastrointestinal issues like constipation and reflux
  • Feeding issues
  • Sleep issues
  • Abnormal brain imaging

MEF2C-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the MEF2C gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both. 

Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.

De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because MEF2C plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that MEF2C-related syndrome is often the result of a de novo variant in MEF2C. Many parents who have had their genes tested do not have the MEF2C genetic variant found in their child who has the syndrome. In some cases, MEF2C-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

MEF2C-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in MEF2C they will likely have symptoms of MEF2C-related syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child or I have a change in the MEF2C gene?

No parent causes their child’s MEF2C-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.

The risk of having another child who has MEF2C-related syndrome depends on the genes of both biological parents. 

  • If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant. 
  • If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent. 

For a symptom-free brother or sister of someone who has MEF2C-related syndrome, the sibling’s risk of having a child who has MEF2C-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing MEF2C-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit MEF2C-related syndrome. 
  • If one biological parent has the same genetic variant causing MEF2C-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has MEF2C-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, 120 people with MEF2C-related syndrome have been identified in a medical clinic. The first case of MEF2C-related syndrome was described in 2010.

People who have MEF2C-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Broad forehead
  • Noticeable ear lobes
  • Tented upper lip
  • Large ears
  • Down slanting palpebral fissures (opening between the eyelids)

Scientists and doctors have only just begun to study MEF2C-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

  • Physical exams and brain studies.
  • Genetics consults.
  • Development and behavior studies.
  • Other issues, as needed.

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

  • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for MEF2C-related syndrome should begin as early as possible, ideally before a child begins school.

If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: www.epilepsy.com/learn/types-seizures.

This section includes a summary of information from major published articles. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and references section of this guide.

Speech and Learning

Most people with MEF2C-related syndrome had developmental delay or intellectual disability. The majority of people had absent speech over the age of 3 years. About 5 people over the age of 5 had a vocabulary of a few words.

  • 96 out of 97 people had developmental delay (99 percent)
  • 83 out of 85 people had intellectual disability (98 percent)
  • 65 out of 70 people were non-verbal over the age of 3 (93 percent)
99%
96 out of 97 people had developmental delay.
98%
83 out of 85 people had intellectual disability.
93%
65 out of 70 people were non-verbal over the age of 3.

Behavior

Most people with MEF2C-related syndrome had autistic-related movements, including hand flapping, hand mouthing, hand clapping, hand biting, hand washing, grasping the midline, and head banging. In addition, people showed a lack of social interest. A few people had self-harming behavior.

  • 46 out of 55 people had features of autism (84 percent)

Brain

Most people with MEF2C-related syndrome had seizures in infancy or childhood. This included different types of seizures, most commonly febrile and myoclonic seizures. Other less common seizure types included generalized tonic-clonic seizures, focal, absent, and infantile spasms.

  • 89 out of 102 people had seizures (87 percent)
  • 55 out of 89 people had seizure onset before 1 year of age (62 percent)
  • 78 out of 89 people had seizure onset before 2 years of age (88 percent)
Human head showing brain outline
87%
89 out of 102 people had seizures.
62%
55 out of 89 people had seizure onset before 1 year of age.
88%
78 out of 89 people had seizure onset before 2 years of age.

Some people had a head size that was smaller than average, also called microcephaly. Many people had an abnormal electroencephalogram (EEG) or brain changes seen on magnetic resonance imaging (MRI).

  • 16 out of 67 people had microcephaly (24 percent)
  • 50 out of 73 people had an abnormal EEG (69 percent)
  • 58 out of 86 people had abnormal MRI findings (67 percent)

Mobility

People who have MEF2C-related syndrome were usually late in developing skills, such as sitting and walking. Most started walking by themselves between 22 months and 8 years. Some people had low muscle tone.

  • 58 out of 59 people had low muscle tone (98 percent)

Feeding and Gastrointestinal

Most people had feeding and digestion issues. This included constipation, feeding difficulties, poor sucking as an infant, frequent vomiting, inability to self-feed, slow gastric emptying, difficulty swallowing, appetite loss, and gastroesophageal reflux disease.

  • 35 out of 36 people had feeding and digestion issues (97 percent)

Heart

Although heart issues are not typically associated with MEF2C-related syndrome, some people had a hole between the left and right upper chambers of the heart (patent foramen ovale) or an opening between two blood vessels leading from the heart (patent ductus arteriosus). There is evidence that MEF2C is important for heart development, so heart issues might be more common in MEF2C-related syndrome.

  • 17 out of 17 people had heart issues (100 percent)

Vision

Eye issues included, but were not limited to, farsightedness (hyperopia), bilateral optic atrophy, crossed eyes (strabismus), nearsightedness (myopia), uncontrolled eye movements (nystagmus), and bilateral esotropia.

  • 24 out of 24 people had vision issues (100 percent)

Sleep

Many people had sleep issues, such as sleeping a lot, sleep disturbances, and irregular sleep patterns.

  • 20 out of 28 people had sleep issues (71 percent)

Where can I find support and resources?

US MEF2C Foundation

MEF2C Foundation

Asociacion MEF2C

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

Sources and References

The content in this guide comes from published studies about MEF2C-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Rocha H. et al. European Journal of Medical Genetics, 59, 478-482, (2016). MEF2C haploinsufficiency syndrome: report of a new MEF2C mutation and review www.pubmed.ncbi.nlm.nih.gov/27255693
  • Borlot F. et al. Seizure, 67, 86-90, (2019). MEF2C-related epilepsy: delineating the phenotypic spectrum from a novel mutation and literature review www.seizure-journal.com/article/S1059-1311(19)30005-6/fulltext
  • Cooley Coleman, J. A., Sarasua, S. M., Boccuto, L., Moore, H. W., Skinner, S. A., & DeLuca, J. M. (2021). Comprehensive investigation of the phenotype of MEF2C-related disorders in human patients: A systematic review. American Journal of Medical Genetics Part A, 185(12), 3884-3894. https://pubmed.ncbi.nlm.nih.gov/34184825/

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