GENE GUIDE

MED13L-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 MED13L-Related Syndrome.
a doctor sees a patient

MED13L-related syndrome is also called impaired intellectual development and distinctive facial features with or without cardiac defects (MRFACD) or MED13L haploinsufficiency syndrome. For this webpage, we will be using the name MED13L-related syndrome to encompass the wide range of variants observed in the people identified.

MED13L-related syndrome happens when there are changes in the MED13L gene. These changes can keep the gene from working as it should.

Key Role

MED13L plays a key role in the growth of the brain and heart. 

Symptoms

Because the MED13L gene is important for brain activity, many people who have MED13L-related syndrome have: 

  • Developmental delay 
  • Intellectual disability 
  • Speech impairments 
  • Changes in facial features 
  • Heart defects 
  • Lower than average muscle tone 
  • Genital defects in males

MED13L-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 MED13L 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 MED13L plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that MED13L-related syndrome is often the result of a de novo variant in MED13L. Many parents who have had their genes tested do not have the MED13L genetic variant found in their child who has the syndrome. In some cases, MED13L-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

MED13L-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in MED13L they will likely have symptoms of MED13L-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 have a change in the MED13L gene?

No parent causes their child’s MED13L-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 MED13L-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 MED13L-related syndrome, the sibling’s risk of having a child who has MED13L-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing MED13L-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit MED13L-related syndrome. 

As of 2024, over 287 people with MED13L-related syndrome have been identified in a medical clinic.

People who have MED13L-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

  • Large tongue 
  • Open mouth 
  • Low-set ears 
  • Flat nasal bridge 
  • Larger than average nose 
  • Wide forehead 
  • Changes in the hands and feet

Scientists and doctors have only just begun to study MED13L-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 MED13L-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: epilepsy.com/…t-is-epilepsy/seizure-types

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 MED13L-related syndrome had developmental delay or intellectual disability, and a speech disorder diagnosis. About 1 in 3 children over age 4 were minimally verbal. 

  • 66 out of 68 people had developmental delay or intellectual disability (97 percent) 
  • 64 out of 66 people had a speech disorder (97 percent) 
  • 15 out of 49 people were minimally verbal over age 4 (31 percent) 

Behavior 

People with MED13L-related syndrome had behavioral issues, including autism, hyperactivity, or attention-deficit/hyperactivity disorder (ADHD). 

  • 28 out of 57 people had autism (49 percent)
  • 13 out of 60 people had hyperactivity (22 percent)
49%
28 out of 57 people had autism.
22%
13 out of 60 people had hyperactivity.

Brain 

People with MED13L-related syndrome had seizures, low muscle tone (hypotonia), high muscle tone (hypertonia), a large head size (macrocephaly), a small head size (microcephaly), or cerebral palsy. 

  • 20 out of 65 people had seizures (31 percent) 
  • 51 out of 61 people had low muscle tone (84 percent) 
  • 8 out of 60 people had high muscle tone (13 percent) 
  • 6 out of 60 people had a large head size (10 percent)
  • 3 out of 60 people had a small head size (5 percent)
Human head showing brain outline
31%
20 out of 65 people had seizures.
84%
51 out of 61 people had low muscle tone.
13%
8 out of 60 people had high muscle tone.
10%
6 out of 60 people had a large head size.
5%
3 out of 60 people had a small head size.

Mobility 

People with MED13L-related syndrome had clumsiness/coordination disorder, movement disorder, and cerebral palsy. 

  • 13 out of 60 people had clumsiness/coordination disorder (22 percent) 
  • 6 out of 60 people had a movement disorder (10 percent)
  • 2 out of 60 people had cerebral palsy (3 percent)
22%
13 out of 60 people had clumsiness/coordination disorder.
10%
6 out of 60 people had a movement disorder.
3%
2 out of 60 people had cerebral palsy.

Digestion issues 

Over one-half of people with MED13L-related syndrome had gastrointestinal issues, such as constipation, gastroesophageal reflux, and diarrhea. 

  • 34 out of 60 people had gastrointestinal issues (57 percent) 

Vision 

Most people had vision issues, and some had issues with frequent ear infections. 

  • 43 out of 60 people had vision issues (72 percent) 
  • 35 out of 60 people had frequent ear infections (58 percent) 

Heart findings 

Rarely, people with MED13L-related syndrome had heart structure issues, such as patent ductus arteriosus, tetralogy of Fallot, and bicuspid aortic valve, as well as other findings. 

  • 11 out of 60 people had heart findings (18 percent)

Where can I find support and resources?

MED13L Syndrome Foundation (US)

MED13L Syndrome Foundation strives to spread awareness, provide family support, and advance medical research in search of a cure for MED13L syndrome.

MED13L Syndrome Association (Europe)

The MED13L SYNDROME association was created in March 2018 at the initiative of three families from Paris and Nantes, who together decided to raise awareness of MED13L syndrome, to bring together families all over the world and to support researchers working on this genetic anomaly and other related anomalies.

MED13L (Germany)

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 MED13L-related syndrome.

  • Carvalho, L. M. L., da Costa, S. S., Campagnari, F., Kaufman, A., Bertola, D. R., da Silva, I. T., Krepischi, A. C. V., Koiffmann, C. P., & Rosenberg, C. (2021). Two novel pathogenic variants in MED13L: One familial and one isolated case. Journal of Intellectual Disability Research, 65(12), 1049-1057. https://pubmed.ncbi.nlm.nih.gov/34713510/
  • Mitchel, M. W., Turner, S., Walsh, L. K., Torene, R. I., Myers, S. M., & Taylor, C. M. (2024). MED13L-related disorder characterized by severe motor speech impairment. Research Square [Preprint]. https://pubmed.ncbi.nlm.nih.gov/39257968/

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