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GENE GUIDE

KDM5B-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 in 2026. 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 KDM5B-Related Syndrome.
a doctor sees a patient

KDM5B-related syndrome is also called intellectual developmental disorder, autosomal recessive 65. For this webpage, we will be using the name KDM5B-related syndrome to encompass the wide range of variants observed in the people identified.

KDM5B-related syndrome happens when there are changes in the KDM5B gene. These changes can keep the gene from working as it should.

Key Role

The KDM5B gene plays an important role in human development.

Symptoms

Because the KDM5B gene is important for brain activity, many people who have KDM5B-related syndrome have:

  • Heart defects
  • Feeding difficulty
  • Global development delay
  • Intellectual disability
  • Speech difficulty
  • Walking issues
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Learning challenges

KDM5B-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 KDM5B 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 KDM5B plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that KDM5B-related syndrome is often the result of a de novo variant in KDM5B. Many parents who have had their genes tested do not have the KDM5B genetic variant found in their child who has the syndrome. In some cases, KDM5B-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

KDM5B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in KDM5B they will likely have symptoms of KDM5B-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

Autosomal recessive conditions

Sometimes a variant in one copy of the KDM5B gene has little or no effect on their health, because one working copy is enough. People who have one working copy of the gene and one non-working copy of the gene are called ‘carriers’. Some people have genes where both copies do not work as they should. In these cases, the person may have inherited non-working copies of the gene from both parents. This can lead to physical issues, developmental issues, or both.

KDM5B-related syndrome can be an autosomal recessive genetic condition. To be affected with symptoms of an autosomal recessive genetic condition, a person has two damaging variants on both copies of their KDM5B. For someone with an autosomal recessive genetic syndrome, every time they have a child they will pass on one non-working copy of KDM5B.

Autosomal Recessive Genetic Syndrome

GENE / gene
Carrier
father
GENE / gene
Carrier
mother
gene / gene
Non-carrier child
GENE / gene
Carrier of the variant
GENE / gene
Carrier of the variant
GENE / GENE
Child with autosomal recessive condition

Why does my child have a change in the KDM5B gene?

No parent causes their child’s KDM5B-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.

Autosomal dominant conditions

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 KDM5B-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 KDM5B-related syndrome, the sibling’s risk of having a child who has KDM5B-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing KDM5B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KDM5B-related syndrome. 
  • If one biological parent has the same genetic variant causing KDM5B-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has KDM5B-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

Autosomal recessive conditions

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 the same biological parents to a child with an autosomal recessive genetic condition, having another child who has RELN-related syndrome is almost always 25 percent.
  • The chance of two carrier parents having a child who is also a carrier is 50 percent. Carriers are not expected to have symptoms. 
  • The chance of them having a child who is not a carrier at all is 25 percent.

For a person who has KDM5B-related syndrome, the risk of having a child who has the same syndrome depends on their partner. 

  • If their partner is a carrier, they have a 50 percent chance of having a child who has the syndrome and a 50 percent chance of having a child who is a carrier. 

If their partner is not a carrier, they have nearly a 0 percent chance of having a child who has the syndrome and a 100 percent chance of having a child who is a carrier.

As of 2026, about 111 people with KDM5B-related syndrome have been identified in a medical clinic.

People with KDM5B-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Rounded end of the nose
  • Thinner than average lips
  • Longer and larger than average head shape
  • Droopy eyelids
  • Eyes that are not aligned

Scientists and doctors have only just begun to study KDM5B-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 KDM5B-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 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.

Researchers are finding that genetic variants in KDM5B associated with autism can be caused by one KDM5B genetic variant or two KDM5B genetic variants.

Below, we have summarized the medical features identified for these two neurodevelopmental conditions.

People with one KDM5B genetic variant (autosomal dominant condition)

Learning and speech

People with autosomal dominant KDM5B-related syndrome had developmental delay or intellectual disability, and speech delays.

  • 19 out of 26 people had developmental delay (73 percent)
  • 11 out of 25 people had intellectual disability (44 percent)
73%
19 out of 26 people had developmental delay
44%
11 out of 25 people had intellectual disability

Behavior

Some people with autosomal dominant KDM5B-related syndrome had behavioral issues, such as features of autism, attention-deficit/hyperactivity disorder (ADHD), anxiety, or aggression.

  • 10 out of 26 people had behavioral issues (39 percent)
  • 13 out of 26 people had features of autism (50 percent)
  • 3 out of 25 people had ADHD (12 percent)

Other developmental features

People with autosomal dominant KDM5B-related syndrome had vision issues, such as crossed eyes (strabismus), joint hypermobility, sleep difficulties, and cardiac and kidney defects. Kidney defects included chronic kidney disease, hydronephrosis, and ureteral dilatation.

  • 5 out of 26 people had vision issues (19 percent)
  • 5 out of 25 people had kidney defects (20 percent)

People with two KDM5B genetic variants (autosomal recessive condition)

Learning and speech

People with autosomal recessive KDM5B-related syndrome had developmental delay or intellectual disability, and speech delays.

  • 9 out of 10 people had developmental delay (90 percent)
  • 8 out of 10 people had intellectual disability (80 percent)
90%
9 out of 10 people had developmental delay
80%
8 out of 10 people had intellectual disability

Behavior

Some people with autosomal recessive KDM5B-related syndrome had behavioral issues, such as features of autism, attention-deficit/hyperactivity disorder (ADHD), or aggression.

  • 2 out of 10 people had behavioral issues (20 percent)
  • 1 out of 10 people had features of autism (10 percent)
  • 1 out of 10 people had ADHD (10 percent)

Other developmental features

People with autosomal recessive KDM5B-related syndrome had vision issues, such as crossed eyes (strabismus), joint hypermobility, and sleep difficulties.

  • 4 out of 10 people had vision issues (40 percent)

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

  • Borroto, M. C., Michaud, C., Hudon, C., Agrawal, P. B., Agre, K., Applegate, C. D., Beggs, A. H., Bjornsson, H. T., Callewaert, B., … & Campeau, P. M. (2024). A genotype/phenotype study of KDM5B-associated disorders suggests a pathogenic effect of dominantly inherited missense variants. Genes (Basel), 15(8), 1033. doi:10.3390/genes15081033
  • Sabetfakhri, N. P., Guter, S. J., Jr., Reyes Pinzon, S. H., Ajilore, O. A., Cook, E. H., & Najjar, F. (2025). de novo KDM5B mutation in a patient with autism spectrum disorder and obsessive-compulsive disorder: Case report. Journal of Mood and Anxiety Disorders, 10, 100114. doi:10.1016/j.xjmad.2025.100114

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