KMT2C-Related Syndrome
KMT2C-related syndrome is also called KMT2C-related neurodevelopmental disorder. For this webpage, we will be using the name KMT2C-related syndrome to encompass the wide range of variants observed in the people identified.
What is KMT2C-related syndrome?
KMT2C-related syndrome happens when there are changes in the KMT2C gene. These changes can keep the gene from working as it should.
Key Role
The KMT2C gene helps to control other genes during brain development.
Symptoms
Because the KMT2C gene is important for brain activity, many people who have KMT2C-related syndrome have:
- Short height
- Poor growth
- Sideways curvature of the spine, also called scoliosis
- Delayed motor development
- Intellectual disability
- Speech delay
- Seizures
- Autism
- Developmental regression
- Brain changes seen on magnetic resonance imaging (MRI)
- Attention-deficit/hyperactivity disorder (ADHD)
- Gastrointestinal issues
- Vision issues
What causes KMT2C-related syndrome?
KMT2C-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 KMT2C 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 KMT2C plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that KMT2C-related syndrome is often the result of a de novo variant in KMT2C. Many parents who have had their genes tested do not have the KMT2C genetic variant found in their child who has the syndrome. In some cases, KMT2C-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
KMT2C-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in KMT2C they will likely have symptoms of KMT2C-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
Why does my child have a change in the KMT2C gene?
No parent causes their child’s KMT2C-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.
What are the chances that other family members of future children will have KMT2C-related syndrome?
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 KMT2C-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 KMT2C-related syndrome, the sibling’s risk of having a child who has KMT2C-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing KMT2C-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KMT2C-related syndrome.
How many people have KMT2C-related syndrome?
As of 2024, over 107 people with KMT2C-related syndrome have been identified in a medical clinic.
Do people who have KMT2C-related syndrome look different?
People who have KMT2C-related syndrome may look different. Appearance can vary and can include some but not all of these features:
- Lower than average muscle tone
- Smaller than average head size
- Flatter than average middle of the face
- Eyebrows that stand out
How is KMT2C-related syndrome treated?
Scientists and doctors have only just begun to study KMT2C-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 KMT2C-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: www.epilepsy.com/learn/types-seizures.
This section includes a summary of information from published articles. It highlights how many people have different symptoms. To learn more about the article, see the Sources and References section of this guide.
Behavior and development concerns linked to KMT2C-related syndrome
Speech and learning
Most people with KMT2C-related syndrome had speech delay and intellectual disability. Few people had mutism (minimal or absent speech).
- 52 out of 65 people had speech delay or language disorder (80 percent)
- 59 out of 69 people had intellectual disability (86 percent)
The severity of intellectual disability (ID) varied among people:
- 24 out of 48 people had mild ID (50 percent)
- 12 out of 48 people had moderate ID (25 percent)
- 12 out of 48 people had severe ID (25 percent)
Behavior
People with KMT2C-related syndrome had behavioral issues, including autism, aggression, hyperactivity, attention-deficit/hyperactivity disorder (ADHD), or obsessive compulsive disorder.
- 48 out of 61 people had autism (79 percent)
- 31 out of 51 people had hyperactivity (61 percent)
- 11 out of 61 people had aggressive behavior (18 percent)
- 9 out of 61 people had obsessive compulsive disorder (15 percent)
Brain
Some people with KMT2C-related syndrome had seizures, low muscle tone (hypotonia), other neurological issues, such as abnormal walking and brain changes seen on magnetic resonance imaging (MRI). Common MRI findings were ventriculomegaly, white-matter defects, and syringomyelia. Six people had developmental regression.
- 10 out of 66 people had seizures (15 percent)
- 19 out of 57 people had hypotonia (33 percent)
- 10 out of 29 people had brain changes seen on MRI (35 percent)
Medical and physical concerns linked to KMT2C-related syndrome
Vision and hearing
People with KMT2C-related syndrome had vision issues, such as strabismus (crossed eyes), and refractive errors (when the shape of the eye causes a blurred image). About 1 out of 4 people had hearing impairments.
- 32 out of 60 people had eye issues (53 percent)
- 12 out of 60 people had strabismus (20 percent)
- 20 out of 60 people had refractive errors (33 percent)
- 17 out of 58 people had hearing impairment (29 percent)
Musculoskeletal defects
About one-half of people with KMT2C-related syndrome had short height. Other less common defects were sideways curvature of the spine (scoliosis), joint hypermobility, and dental changes.
- 39 out of 71 people had short height (55 percent)
- 10 out of 64 people had scoliosis (16 percent)
- 5 out of 64 people had joint hypermobility (8 percent)
- 13 out of 70 people had dental changes (19 percent)
Feeding and digestion issues
People had gastrointestinal issues, such as constipation and feeding issues.
- 23 out of 43 people had gastrointestinal issues (54 percent)
- 6 out of 43 people had constipation (14 percent)
Other medical features
Some people with KMT2C-related syndrome had heart structure defects and less commonly genitourinary defects present at birth. Heart defects included valve defects and atrial septal defect.
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.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on KMT2C: www.simonssearchlight.org/research/what-we-study/KMT2C
- Simons Searchlight KMT2C Facebook community: https://www.facebook.com/groups/KMT2C
Sources and References
The content in this guide comes from a published study about KMT2C-related syndrome. Below you can find details about the study, as well as links to summaries or, in some cases, the full article.
- Rots, D., Choufani, S., Faundes, V., Dingemans, A. J. M., Joss, S., Foulds, N., Jones, E. A., Stewart, S., Vasudevan, P., … & Banka, S. (2024). Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes. American Journal of Human Genetics, 111(8), 1626-1642. https://pubmed.ncbi.nlm.nih.gov/39013459/