GENE GUIDE

KDM3B-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 KDM3B-Related Syndrome.
a doctor sees a patient

KDM3B-related syndrome happens when there are changes to the KDM3B gene. These changes can keep the gene from working as it should.

Key Role

The KDM3B gene plays a key role in brain development.

Because the KDM3B gene is important in the development and function of brain cells, many people who have KDM3B-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Behavioral concerns

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the KDM3B 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 KDM3B plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that KDM3B-related syndrome is often the result of a de novo change in KDM3B. Many parents who have had their genes tested do not have the KDM3B gene change found in their child who has the syndrome. In some cases, KDM3B-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.

Child who has genetic change in KDM3B gene

Genetic change occurs in egg or sperm after fertilization
Child with de novo genetic change in autism gene

Why does my child have a change in the KDM3B gene?

No parent causes their child’s KDM3B-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 KDM3B-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 KDM3B-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 KDM3B-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 KDM3B-related syndrome is 50 percent.

For a person who has KDM3B-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2019, about 17 people in the world with changes in the KDM3B gene had been described in the medical literature. The first case of KDM3B- related syndrome was described in 2019. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have KDM3B-related syndrome may be short.

Scientists and doctors have only just begun to study KDM3B-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 KDM3B-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 a published article describing 14 people who have the condition and 3 of their parents. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Learning

Almost everyone in the study had developmental delay or intellectual disability.

  • 16 out of 17 people had developmental delay or intellectual disability.

Behavior 

About half had behavioral concerns. 25 percent had Attention Deficit Hyperactivity Disorder (ADHD). 20 percent had autism.

  • 8 out of 15 people had behavioral concerns.
  • 4 out of 16 people had ADHD.
  • 3 out of 15 people had autism.

 

94%
16 out of 17 people had developmental delay or intellectual disability.
53%
8 out of 15 people had behavioral concerns.
25%
4 out of 16 people had ADHD.
20%
3 out of 15 people had autism.

Feeding and digestion issues

More than half of those in the study had feeding difficulties as infants.

  • 9 out of 15 people had feeding difficulties.

Growth

Half were short.

  • 8 out of 16 people were short.

Muscle tone

Nearly 40 percent had low muscle tone.

  • 5 out of 13 people had low muscle tone.

Brain

20 percent had seizures.

  • 3 out of 15 people had seizures.

Potential cancer risk

Two out of 17 people who had KDM3B-related syndrome had childhood cancers: one had a type of blood cancer called acute myeloid leukemia at age 13, and another had an immune system cancer called Hodgkin lymphoma at age 17. At this point, it is unclear whether changes in the KDM3B gene contributed to their cancers. Scientists hope that studying more people who have KDM3B-related syndrome will help us understand whether this syndrome is linked to cancer.

60%
9 out of 15 people had feeding difficulties.
50%
8 out of 16 people were short.
38%
5 out of 13 people had low muscle tone.
20%
3 out of 15 people had seizures.

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 a published study about KDM3B-related syndrome. Below you can find details about the study, as well as links to summaries or, in some cases, the full article.

  • Diets IJ. et al. American Journal of Human Genetics, 104, 758-766, (2019). De novo and inherited pathogenic variants in KDM3B cause intellectual disability, short stature, and facial dysmorphism www.ncbi.nlm.nih.gov/pubmed/30929739

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