EHMT1-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 EHMT1-Related Syndrome.
a doctor sees a patient

EHMT1-related syndrome is also called Kleefstra syndrome 1. For this webpage, we will be using the name EHMT1-related syndrome to encompass the wide range of variants observed in the people identified.

EHMT1-related syndrome happens when there are changes in the EHMT1 gene. These changes can keep the gene from working as it should.

Key Role

The EHMT1 gene plays a role in modifying the shape of chromosomes. Chromosomes are the structures that house DNA within our cells. By modifying the chromosome, the EHMT1 enzyme can turn other genes on or off.


Because the EHMT1 gene is important in controlling gene expression, many people who have EHMT1-related syndrome have:

  • Intellectual disability
  • Autism or features of autism
  • Speech delay
  • Seizures
  • Sleep difficulties
  • Behavior issues, such as aggression, and obsessive compulsive disorder
  • Obesity
  • Heart and/or kidney defects
  • Hearing loss
  • Vision issues
  • Recurrent respiratory infections
  • Genital defects in males
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Extreme lack of interest or lack of movement and communication, which happens after puberty

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the EHMT1 gene: one copy from their mother, from the egg, and one copy from their father, from the sperm. 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.

Sometimes a random change happens in the sperm or egg. 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 EHMT1 plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that EHMT1-related syndrome is often the result of a de novo change in EHMT1. Many parents who have had their genes tested do not have the EHMT1 gene change found in their child who has the syndrome. In some cases, EHMT1-related syndrome happens because the gene change was passed down from a parent. This is called dominant inheritance.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change

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

No parent causes their child’s EHMT1-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 EHMT1-related syndrome depends on the genes of both birth parents.

  • If neither birth parent has the same gene change 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 change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has EHMT1-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 EHMT1-related syndrome.
  • If one birth parent has the same gene change found in their 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 child who has EHMT1-related syndrome is 50 percent.

For a person who has EHMT1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 183 people with EHMT1-related syndrome have been identified in a medical clinic. The first case of EHMT1-related syndrome was described in 2006.

People who have EHMT1-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower than average muscle tone
  • Flatter than average face
  • Smaller than average head size
  • Wide-set eyes
  • Arched eyebrows
  • Outward facing lower lip

Scientists and doctors have only just begun to study EHMT1-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 EHMT1-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:

This section includes a summary of information from a major published article describing about 100 people who have the syndrome. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.


Most people had intellectual disability ranging from moderate to severe, and required special education support. Rarely, some people had mild intellectual disability or average IQ. Most people had autism and speech delays.


Some people had seizures, including tonic-clonic seizures, absence seizures, and complex partial epilepsy.

  • 30 percent of people had seizures

Developmental formation issues

Developmental formation issues are common for people with EHMT1-related syndrome. Consults with specialists may be required.

  • 50 percent of people with EHMT1-related syndrome had a heart defect
  • 10 to 30 percent of people had kidney defects
  • 30 percent of males had microgenitalia
50 percent of people with EHMT1-related syndrome had a heart defect.
Up to 30 percent of people had kidney defects.
30 percent of males had microgenitalia.


About one-half of people with EHMT1-related syndrome had obesity.

Where can I find support and resources?


IDefine is a nonprofit organization dedicated to discovering life-changing treatments and cures for those with intellectual disabilities stemming from genetic disorders.

We plan to discover and bring to market life-changing treatments for Kleefstra Syndrome patients. In doing so, we will demonstrate that Intellectual Disability (ID) disorders are in fact treatable conditions, in the same way that disorders of mental illness have become treatable with drugs over time.

The Kleefstra syndrome community stretches rights across the world and is growing.  Kleefstra Syndrome UK exists to offer support, education, and awareness of this rare condition.  Over 700 families currently benefit from our community support network.

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 a published study about EHMT1-related syndrome. Below you can find details about the study, as well as a link to a summary.

  • Ciaccio C. et al. Cytogenetic and Genome Research, 156, 127-133, (2018). New insights into Kleefstra syndrome: Report of two novel cases with previously unreported features and literature review.
  • Kleefstra T, & de Leeuw N. Kleefstra Syndrome. 2023 Jan 26. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from:
  • Vermeulen, K., de Boer, A., Janzing, J. G. E., Koolen, D. A., Ockeloen, C. W., Willemsen, M. H., Verhoef, F. M., van Deurzen, P. A. M., van Dongen, L., van Bokhoven, H., Egger, J. I. M., Staal, W. G., & Kleefstra, T. (2017). Adaptive and maladaptive functioning in Kleefstra syndrome compared to other rare genetic disorders with intellectual disabilities. American Journal of Medical Genetics Part A, 173(7), 1821-1830.

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