GENE GUIDE

KMT5B-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 KMT5B-Related Syndrome.
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KMT5B-related syndrome is also called intellectual developmental disorder, autosomal dominant 51. For this webpage, we will be using the name KMT5B-related syndrome to encompass the wide range of variants observed in the people identified.

KMT5B-related syndrome happens when there are changes to the KMT5B gene. These changes can keep the gene from working as it should.

Key Role

The KMT5B gene plays a key role in brain development.

Symptoms

Because the KMT5B gene is important for brain activity, many people who have KMT5B-related syndrome have:

  • Intellectual disability
  • Global developmental delay
  • Autism
  • Speech delay
  • Seizures
  • Lower than average muscle tone

KMT5B-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 KMT5B 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 KMT5B plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that KMT5B-related syndrome is often the result of a de novo variant in KMT5B. Many parents who have had their genes tested do not have the KMT5B genetic variant found in their child who has the syndrome. In some cases, KMT5B-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

KMT5B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in KMT5B they will likely have symptoms of KMT5B-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 KMT5B gene?

No parent causes their child’s KMT5B-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 KMT5B-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 KMT5B-related syndrome, the sibling’s risk of having a child who has KMT5B-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing KMT5B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KMT5B-related syndrome.

As of 2024, at least 59 people with KMT5B-related syndrome have been described in medical research. The first case of KMT5B-related syndrome was described in 2012. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have KMT5B-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower than average muscle tone
  • Broad forehead
  • Long, oval face

Scientists and doctors have only just begun to study KMT5B-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 KMT5B-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/learn/types-seizures.

This section includes a summary of information from a published article describing four people who have the syndrome. To learn more about the article, see the Sources and references section of this guide.

Learning

All people with KMT5B-related syndrome had developmental delay or intellectual disability.

  • 59 out of 59 people had developmental delay or intellectual disability (100 percent)

Behavior

Many people with KMT5B-related syndrome had behavioral challenges, such as autism or features of autism.

  • 25 out of 46 people had autism or features of autism (54 percent)

Brain

Some people with KMT5B-related syndrome had seizures, brain changes on magnetic resonance imaging (MRI), and a larger than average head size, also called macrocephaly.

  • 15 out of 45 people had seizures (33 percent)
  • 11 out of 30 people had brain changes seen on MRI (37 percent)
  • 31 out of 53 people had macrocephaly (59 percent)
33%
15 out of 45 people had seizures.
37%
11 out of 30 people had brain changes seen on MRI.
59%
31 out of 53 people had macrocephaly.

Physical features

Some people with KMT5B-related syndrome had lower than average muscle tone, tall height, short height, overgrowth, or a broad forehead. Facial changes were common, including having a long face, arched eyebrows, widely spaced eyes, noticeable ears, and a mild underbite.

  • 22 out of 27 people had lower than average muscle tone (82 percent)
  • 3 out of 17 people had tall height (18 percent)
  • 9 out of 43 people had short height (21 percent)
  • 5 out of 16 people had overgrowth (31 percent)
  • 5 out of 15 people had a broad forehead (33 percent)
  • 31 out of 39 people had unique facial features (80 percent)
82%
22 out of 27 people had lower than average muscle tone.
18%
3 out of 17 people had tall height.
21%
9 out of 43 people had short height.
31%
5 out of 16 people had overgrowth.
33%
5 out of 15 people had a broad forehead.
80%
31 out of 39 people had unique facial features.

Other medical findings

Some people with KMT5B-related syndrome had heart defects, such as atrial or ventricular septal defects, or strabismus (crossed eyes).

  • 8 out of 31 people had heart defects (26 percent)
  • 5 out of 16 people had strabismus (31 percent)

Where can I find support and resources?

KMT5B Gene Facebook Group

www.facebook.com/groups/163843164229102

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 a published study about KMT5B-related syndrome. Below you can find details about the study, as well as a link to a summary and the full article.

  • Faundes V. et al. American Journal of Human Genetics, 102, 175-187, (2018). Histone lysine methylases and demethylases in the landscape of human developmental disorders www.ncbi.nlm.nih.gov/pubmed/29276005
  • Eliyahu, A., Barel, O., Greenbaum, L., Zaks Hoffer, G., Goldberg, Y., Raas-Rothschild, A., Singer, A., Bar-Joseph, I., Kunik, V., … & Pode-Shakked, B. (2022). Refining the phenotypic spectrum of KMT5B-associated developmental delay. Frontiers in Pediatrics, 10, 844845. https://pubmed.ncbi.nlm.nih.gov/35433545/
  • Sheppard, S. E., Bryant, L., Wickramasekara, R. N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C. J., Faundes, V., … & Stessman, H. A. F. (2023). Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice. Science Advances, 9(10), eade1463. https://pubmed.ncbi.nlm.nih.gov/36897941/

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