National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

MED13L haploinsufficiency syndrome

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Other Names:
Cardiac anomalies-developmental delay-facial dysmorphism syndrome; Intellectual disability and distinctive facial features with or without cardiac defects; MED13L syndrome
MED13L haploinsufficiency syndrome is a genetic syndrome that causes intellectual disability, speech problems, and behavioral problems. People with the syndrome usually have distinctive facial features, such as eyes that slant upwards, a flat nasal bridge with a bulb-like tip, very small chin (micrognathia), large and lowset ears, and broad forehead.[1] Most children with the syndrome have poor muscle tone (hypotonia) and may take longer to learn to sit and walk independently (delayed motor skills). Some babies with MED13L haploinsufficiency syndrome are born with heart defects, which may be mild or severe. Other features may include short stature, cleft palate, problems with coordination (ataxia), and recurrent seizures (epilepsy).[2][3]

MED13L haploinsufficiency syndrome is caused by changes (pathogenic variants, also called mutations) in the MED13L gene. Diagnosis may be suspected due to distinctive facial features, speech delay, and intellectual disability, but must be confirmed by genetic testing.[4] There is no cure or specific treatment for MED13L haploinsufficiency syndrome. Treatment depends on the types and severity of the medical, developmental, and behavioral problems affecting the person with the syndrome and may include heart surgery and therapies such as speech, occupational, and behavioral therapy.[5]
Last updated: 5/28/2018
Clinical features of MED13L haploinsufficiency syndrome include intellectual disability, speech problems, distinctive facial features, and developmental delay. The facial features may be noticeable at birth and most commonly include eyes that slant upwards, a flat nasal bridge with a bulb-like tip, very small chin (micrognathia), large and lowset ears, and broad forehead. A large tongue (macroglossia) and horizontal eyebrows may also be present. Children with the syndrome may tend to keep their mouth open to varying degrees. As babies with the syndrome grow, they usually are delayed in meeting milestones, such as sitting and walking independently. Speech is almost always delayed and speech problems may be severe. Most babies and children with the syndrome also have weak muscle tone (hypotonia). Intellectual disability usually ranges from mild to moderate. Developmental delays can range from mild to severe.[1][2][3][5]

Some infants with MED13L haploinsufficiency syndrome are born with heart defects, because the heart did not form properly. In some cases, the heart defects are mild, such as a patent foramen ovale, but in other cases, the heart defects may be more severe, such as transposition of the great arteries. 

Other features of MED13L haploinsufficiency syndrome may include being shorter than other family members and peers (short stature), cleft palate, problems with coordination (ataxia), and recurrent seizures (epilepsy).[2][3] Some people with the syndrome have severe symptoms, while others may be more mildly affected.[5] 
Last updated: 5/28/2018
MED13L haploinsufficiency syndrome is caused by a change (pathogenic variant also called mutation) in one copy of the MED13L gene. This gene provides the body with instructions for making a protein that helps the brain and the heart develop correctly.[6]

Like most genes, MED13L comes in a pair (two copies). When one copy of this gene has a pathogenic variant, only one copy is working in the body (haploinsufficiency). Haploinsufficiency of MED13L causes the brain and sometimes the heart to not develop normally. This causes the different features associated with MED13L haploinsufficiency syndrome.[6]
Last updated: 5/28/2018
In most cases, MED13L haploinsufficiency  syndrome is not inherited from a parent, but is instead present for the first time in a person who is diagnosed with the syndrome. This kind of genetic change is known as a de novo pathogenic variant (mutation).[1]

There have been some documented cases in which a person with this syndrome does inherit it from one parent. This may happen if the parent also has MED13L haploinsufficiency syndrome, but it was never diagnosed because the clinical features are mild in the parent. In this case, each child of the parent with MED13L pathogenic variant would have a 50% chance to inherit the syndrome. However, the clinical features in the child may be mild like the parent’s or the features may be more severe. The syndrome can also be inherited when some of the cells in the parent’s body has the pathogenic variant in MED13L, but most do not. In this case, the parent would have no clinical features of the syndrome, but each future child would be at an increased risk to have the syndrome.[7] 
Last updated: 5/28/2018
A doctor may suspect MED13L haploinsufficiency syndrome based on a baby, child, or even adult having the distinctive facial features, speech problems, and intellectual disability common to the syndrome. The diagnosis must be confirmed by finding a pathogenic variant in the MED13L gene through genetic testing, since many other genetic syndromes can cause similar clinical features.[5] 
Last updated: 5/28/2018
There is no cure for MED13L haploinsufficiency syndrome. Treatment is based on the type and severity of medical, developmental, and behavioral problems present in the infant, child, or adult with the syndrome. For example, an infant with a heart defect may need surgery to correct the problem. Other possible treatment options include behavioral, speech, and occupational therapy to help the person with MED13L haploinsufficiency syndrome to achieve their fullest potential.[5] 
Last updated: 5/28/2018

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with MED13L haploinsufficiency syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for MED13L haploinsufficiency syndrome:
    Simons SearchLight
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss MED13L haploinsufficiency syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Kniffin CL. Mental Retardation and Distinctive Facial Features With or Without Cardiac Defects; MRFACD. Online Mendelian Inheritance in Man. February 5, 2016; https://www.omim.org/entry/616789.
  2. Asadollahi R & cols. Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability. European Journal of Human Genetics. 2013; 21(10):1100-1104. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778355/.
  3. Asadollahi R, Zweier M, Gogoll L, Schiffmann R, Sticht H, Steindl K, and Rauch A. Genotype-phenotype evaluation of MED13L defects in the light of a novel truncating and a recurrent missense mutation. European Journal of Medical Genetics. September 2017; 60(9):451-464. https://www.ncbi.nlm.nih.gov/pubmed/28645799.
  4. Van Haelst MM & cols. Further confirmation of the MED13L haploinsufficiency syndrome. European Journal of Human Genetics. 2015; 23(1):135-138. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266749/.
  5. Adegbola & cols. Redefining the MED13L syndrome. Eur J Hum Genet. October, 2015; 23(10):1308-17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592099/.
  6. MED13L mediator complex subunit 13 like [Homo sapiens (human)]. Gene. June 4, 2017; https://www.ncbi.nlm.nih.gov/gene/23389.
  7. Yamamoto T, Shimojima K, Ondo Y, Shimakawa S, and Okamoto N. MED13L haploinsufficiency syndrome: A de novo frameshift and recurrent intragenic deletions due to parental mosaicism. American Journal of Medical Genetics. May 2017; 173(5):1264-1269. https://www.ncbi.nlm.nih.gov/pubmed/28371282.