MED12-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 MED12-Related Syndrome.
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MED12-related syndrome is also called Hardikar syndrome, Lujan syndrome, X-linked Ohdo syndrome, FG syndrome type 1, Opitz-Kaveggia syndrome, and nonspecific intellectual disability. For this webpage, we will be using the name MED12-related syndrome to encompass the wide range of variants observed in the people identified. 

MED12-related syndrome happens when there are changes in the MED12 gene. These changes can keep the gene from working as it should. 

Key Role

The MED12 gene plays an important role in the development of the brain. 


Because the MED12 gene is important for many parts of the body, some people may have: 

  • Intellectual disability, mild to moderate 
  • Developmental delay 
  • Autism or features of autism 
  • Behavior issues, such as aggressive behavior or obsessive compulsive disorder 
  • Brain changes seen on magnetic resonance imaging (MRI) 
  • Heart development defects 
  • Hearing issues 
  • Feeding issues and intestinal development issues 

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Genes are arranged in structures in our cells called chromosomes. Chromosomes and genes usually come in pairs, with one copy from the mother, from the egg, and one copy from the father, from the sperm.

We each have 23 pairs of chromosomes. One pair, called the X and Y chromosomes, differs between biological males and biological females. Biological females have two copies of the X chromosome and all its genes, one from their mother and one from their father.

Biological males have one copy of the X chromosome and all of its genes, from their mother, and one copy of the Y chromosome and its genes, from their father. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

The MED12 gene is located on the X chromosome, so changes in this gene can affect biological males and biological females in different ways. Biological males who have changes in this gene will likely have MED12-related syndrome. Biological females will likely have MED12-related syndrome if they have changes in both copies of the gene.

Biological females who have one working copy of the gene and one non-working copy of the gene are called ‘carriers’. This means that they may not have signs or symptoms of the syndrome, but they can pass it along to their children. Research shows that some cases of MED12-related syndrome are inherited.

In other cases, it results from a random change in the MED12 gene in the sperm or egg during development. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the gene change. De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because MED12 plays a key role in development, de novo changes in this gene can have a meaningful effect.

Why does my child have a change in the MED12 gene?

No parent causes their child’s MED12-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 MED12-related syndrome depends on the genes of both birth parents.

  • Biological females who have changes in the MED12 gene and are pregnant with a daughter have a 50 percent chance of passing on the gene change and a 50 percent chance of passing on the working copy of the gene. If they are pregnant with a son, the child has a 50 percent chance of inheriting the gene change and the syndrome.

For a symptom-free sibling, a brother or sister, of someone who has MED12-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

  • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has MED12-related syndrome.
  • If the mother has the same gene change found in her child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a son who has MED12-related syndrome is 50 percent.

For a person who has MED12-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, about 84 people in the world with MED12-related syndrome have been identified in the medical clinic.

People who have MED12-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

  • Lower than average muscle tone 
  • Finger growth defects 
  • Lower than average height 
  • Larger than average head size 
  • Noticeable nose 
  • Cleft lip or palate 
  • Eyes that are not aligned 

Scientists and doctors have only just begun to study MED12-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 MED12-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:…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.

Diagnoses of the different MED12 syndromes are completed through the various clinical findings. More details are provided below for the various known clinical syndromes.

The MED12 gene is located on the X chromosome, and for some of the syndromes, female carriers do not usually have medical features – it depends on the genetic variant. To date, not all genetic variants have a clear link to a resulting clinical diagnosis. 

Hardikar syndrome  

People with Hardikar syndrome often have cleft lip or palate, liver issues and liver disease, intestinal issues, retina degeneration, narrow aorta of the heart, swelling of the kidneys, a cyst in the duct attached to the liver, and intellectual abilities that are within normal range. Most people do not have developmental delay. 

All people with Hardikar syndrome are females with a MED12 frameshift or nonsense variants.  

Lujan syndrome 

People with Lujan syndrome have a specific MED12 variant called p.Asn1007Ser. Most people with Lujan syndrome have mild to moderate intellectual disability and speech that is in a high nasal range. Males often have a long thin appearance in their height, fingers, and toes. 

Female carriers of Lujan syndrome are not expected to have symptoms. Other variants that have been suggested to be linked to Lujan syndrome include: p.Arg1214Cys, p.Arg1295His, and p.Trp1557Arg. 

X-linked Ohdo syndrome 

People with x-linked Ohdo syndrome often have intellectual disability, narrow eye openings, droopy eyelids, a small jaw, dental findings, and a triangle-shaped face. Some people might have a smaller than average head size and shorter than average height. Many people with x-linked Ohdo syndrome might not develop the ability to speak, have hearing loss, have hyper mobile joints, and have hyperactivity. 

Usually, males with x-linked Ohdo syndrome have a de novo, new variant, or inherited variant from an unaffected mother. Although, affected mothers have been found. 

Medical features associated with the MED12 genetic variant are thought to more or less happen in a female due to a process called X inactivation. This is a random process where a cell chooses one X chromosome to silence gene expression. This means that if the X chromosome that has the MED12 genetic variant is being silenced or turned off, this person may be more likely to have medical features. 

Variants that have been suggested to be associated with x-linked Ohdo syndrome include: p.Glu172Gln, p.Arg296Glu, and p.Arg1148His. But, some of these variants have been associated with other MED12-related syndromes. 

FG syndrome type 1 or Opitz-Kaveggia syndrome 

FG syndrome type 1 is also known as Opitz-Kaveggia syndrome. People with FG syndrome type 1 often have neurodevelopmental delays; facial features that include larger than average head size and wide-spaced eyes; broad thumbs; organ formation issues, such as intestinal, heart, or skeletal issues; and eager to please behavior. In addition, people with FG syndrome type 1 are usually larger than average, have a larger than average head size, and have borderline to average or above average intelligence. 

Female carriers are not expected to have symptoms. Common variants associated with FG syndrome type 1 include: p.Gly958Glu, and p.Arg961Trp.  

Nonspecific intellectual disability 

The medical features of nonspecific intellectual disability caused by a MED12 genetic variant are not consistent with one of the above MED12-related syndromes. Feeding issues are relatively common, as well as bone and development defects. Facial features in people diagnosed with nonspecific intellectual disability overlap with the other MED12-related syndromes. Defects in head size are not common in females. 

Males and female carriers with damaging MED12 variants have been diagnosed with nonspecific intellectual disability. A range of variants are possible and these include missense variants and frameshift or nonsense variants have been diagnosed in people with nonspecific intellectual disability. 

Where can I find support and resources?

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 and click “Join Us.”

Sources and References

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

  • Lyons MJ. MED12-Related Disorders. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 23, 2008. 
  • Maia N, Ibarluzea N, Misra-Isrie M, et al. Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes. Am J Med Genet A. 2023;191(1):135-143. doi:10.1002/ajmg.a.63004

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