GENE GUIDE

MEIS2-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 MEIS2-Related Syndrome.
a doctor sees a patient

MEIS2-related syndrome happens when there are changes in the MEIS2 gene. These changes can keep the gene from working as it should.

Key Role

The MEIS2 gene plays a key role in the development of the brain and the heart. 

Symptoms

Because the MEIS2 gene is important for brain activity, many people who have MEIS2-related syndrome have: 

  • Cleft palate, which is an opening or split in the upper lip or roof of the mouth that occurs before birth 
  • Developmental delay 
  • Intellectual disability 
  • Behavioral issues 
  • Changes in the heart structure 
  • Feeding issues

MEIS2-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 MEIS2 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 MEIS2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that MEIS2-related syndrome is often the result of a de novo variant in MEIS2. Many parents who have had their genes tested do not have the MEIS2 genetic variant found in their child who has the syndrome. In some cases, MEIS2-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

MEIS2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in MEIS2 they will likely have symptoms of MEIS2-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 MEIS2 gene?

No parent causes their child’s MEIS2-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 MEIS2-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 MEIS2-related syndrome, the sibling’s risk of having a child who has MEIS2-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing MEIS2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit MEIS2-related syndrome. 

As of 2024, over 49 people with MEIS2-related syndrome have been identified in a medical clinic. 

People who have MEIS2-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

  • Arched eyebrows 
  • Broad forehead with a noticeable ridge

Scientists and doctors have only just begun to study MEIS2-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 MEIS2-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.

Research suggests that people who have missense variants in the MEIS2 gene might have more complicated medical features compared with people who have an MEIS2 deletion variant or MEIS2 loss of function variant. 

Some people inherit the MEIS2 variant from a parent who may or may not have medical features. 

Speech and learning 

People with MEIS2-related syndrome had developmental delay or intellectual disability, and speech issues. Most people were able to walk by the age of 3. 

  • 18 out of 35 people had developmental delay or intellectual disability (51 percent)
  • 7 out of 11 people had a speech disorder (64 percent)
51%
18 out of 35 people had developmental delay or intellectual disability.
64%
7 out of 11 people had a speech disorder.

Behavior 

People with MEIS2-related syndrome had behavioral issues, including autism.  

  • 9 out of 11 people had autism (82 percent) 

Brain 

Some people with MEIS2-related syndrome had a small head size (microcephaly), and few had brain changes seen on magnetic resonance imaging (MRI). 

  • 10 out of 26 people had a small head size (38 percent)
Human head showing brain outline

Heart 

Over one-half of people with MEIS2-related syndrome had congenital heart defects, most commonly a hole in the heart (septal defects). 

  • 15 out of 28 people had congenital heart defects (54 percent) 

Mouth and feeding issues 

Often people had cleft lip or palate formation changes, and feeding or digestion issues. 

  • 19 out of 26 people had cleft lip or palate changes (73 percent) 
  • 8 out of 11 people had feeding or digestion issues (73 percent) 

Vision 

Some people with MEIS2-related syndrome had vision issues, such as myopia (nearsightedness) or strabismus (crossed eyes).

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 www.simonssearchlight.org and click “Join Us.”

Sources and References

The content in this guide comes from published studies about MEIS2-related syndrome.

  • Gangfuß, A., Yigit, G., Altmüller, J., Nürnberg, P., Czeschik, J. C., Wollnik, B., Bögershausen, N., Burfeind, P., Wieczorek, D., … & Kuechler, A. (2021). Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study. American Journal of Medical Genetics Part A, 185(4), 1216-1221. https://pubmed.ncbi.nlm.nih.gov/33427397/
  • Giliberti, A., Currò, A., Papa, F. T., Frullanti, E., Ariani, F., Coriolani, G., Grosso, S., Renieri, A., & Mari, F. (2020). MEIS2 gene is responsible for intellectual disability, cardiac defects and a distinct facial phenotype. European Journal of Medical Genetics, 63(1), 103627. https://pubmed.ncbi.nlm.nih.gov/30735726/
  • Verheije, R., Kupchik, G. S., Isidor, B., Kroes, H. Y., Lynch, S. A., Hawkes, L., Hempel, M., Gelb, B. D., Ghoumid, J., … & Breckpot, J. (2019). Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability. European Journal of Human Genetics, 27(2), 278-290. https://pubmed.ncbi.nlm.nih.gov/30291340/
  • Zhang, B., Liu, M., Fong, C. T., & Iqbal, M. A. (2021). MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: Documentation of mosaicism in an unaffected parent. Molecular Cytogenetics, 14(1), 58. https://pubmed.ncbi.nlm.nih.gov/34930369/

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