Rare Pediatrics News

Disease Profile

MED13L haploinsufficiency syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Cardiac anomalies-developmental delay-facial dysmorphism syndrome; Intellectual disability and distinctive facial features with or without cardiac defects; MED13L syndrome

Summary

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]

Symptoms

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] 

Cause

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]

Diagnosis

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] 

Treatment

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] 

Organizations

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.

Learn more

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.

    References

    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. https://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. https://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.

    Rare Pediatrics News