GENE GUIDE

KDM6B-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 KDM6B-Related Syndrome.
a doctor sees a patient

KDM6B-related syndrome is also called Stolerman neurodevelopmental syndrome, Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (NEDCFSA) or KDM6B-related neurodevelopmental disorder. For this webpage, we will be using the name KDM6B-related syndrome to encompass the wide range of variants observed in the people identified.

KDM6B-related syndrome happens when there are changes to the KDM6B gene. These changes can keep the gene from working as it should.

Key Role

The KDM6B gene plays a role in brain development.

Symptoms

Because the KDM6B gene is important in brain development and function, many people who have KDM6B-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Autism
  • Motor delays
  • Speech delays
  • Attention deficit hyperactivity disorder, or ADHD
  • Lower than average muscle tone
  • Stiffness and movement abnormalities
  • Sleep issues
  • Feeding difficulties

KDM6B-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 KDM6B 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 KDM6B plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that KDM6B-related syndrome is often the result of a de novo variant in KDM6B. Many parents who have had their genes tested do not have the KDM6B genetic variant found in their child who has the syndrome. In some cases, KDM6B-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

KDM6B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in KDM6B they will likely have symptoms of KDM6B-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 KDM6B gene?

No parent causes their child’s KDM6B-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 KDM6B-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 KDM6B-related syndrome, the sibling’s risk of having a child who has KDM6B-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing KDM6B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KDM6B-related syndrome. 

As of 2024, at least 90 people with KDM6B-related syndrome have been described in the medical literature. The first case of KDM6B-related neurodevelopmental disorder was described in 2019.

People who have KDM6B-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower than average muscle tone
  • Unusually large range of movement in joints
  • Wide hands or feet
  • Noticeable bridge of nose
  • Fingers or toes that are webbed or joined, also called syndactyly
  • Larger than average head size
  • Spots of different pigmentation of the skin
  • More prominent forehead and fuller cheeks
  • Larger and or misshapen ears
  • Deeper set eyes
  • Eyes that do not align

Scientists and doctors have only just begun to study KDM6B-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 KDM6B-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.

Speech and Learning

Most people with KDM6B-related syndrome had developmental delay or intellectual disability. Some children had speech delays.

  • 42 out of 66 people had developmental delay or intellectual disability (64 percent)
  • 72 out of 79 had speech delays (91 percent)

Behavior

Many people with KDM6B-related syndrome had behavioral concerns, attention-deficit/hyperactivity disorder (ADHD), and autism.

  • 44 out of 73 people had behavioral concerns (60 percent)
  • 31 out of 73 people had ADHD (42 percent)
  • 51 out of 79 people had autism or features of autism (65 percent)
60%
44 out of 73 people had behavioral concerns.
42%
31 out of 73 people had ADHD.
65%
51 out of 79 people had autism or features of autism.

Brain

Some people with KDM6B-related syndrome had seizures and sleeping issues, motor delays and low muscle tone were more common. One out of three people with KDM6B-related syndrome had nonspecific findings on brain magnetic resonance imaging (MRI).

  • 11 out of 70 people had seizures (16 percent)
  • 21 out of 68 people had issues sleeping (31 percent)
  • 67 out of 75 people had motor delay (89 percent)
  • 40 out of 72 people had low muscle tone, also called hypotonia (56 percent)
  • 16 out of 67 people had a movement disorder or ataxia (24 percent)
  • 15 out of 46 people had nonspecific MRI abnormalities (33 percent)
Human head showing brain outline
16%
11 out of 70 people had seizures.
31%
21 out of 68 people had issues sleeping.
89%
67 out of 75 people had motor delay.
56%
40 out of 72 people had hypotonia.
24%
16 out of 67 people had a movement disorder or ataxia.
33%
15 out of 46 people had nonspecific MRI findings.

Gastrointestinal

Issues with feeding and digestion happened in some people with KDM6B-related syndrome. Digestion issues included gastroesophageal reflux disease (GERD) and constipation.

  • 19 out of 65 people had GERD (29 percent) 
  • 13 out of 64 people had constipation (20 percent) 
  • 25 out of 64 people had neonatal feeding difficulties (39 percent) 

Growth

  • 17 out of 65 people had a larger than average head size (26 percent)
  • 21 out of 69 people had at least one feature of overgrowth (30 percent)

Bone and Joint 

About half of people experienced more relaxed joints and some had fingers, fingertips, hands, toes or feet that were more broad in appearance. 

  • 28 out of 64 people had joint laxity (44 percent) 
  • 19 out of 68 people had broad fingers, fingertips, hands, toes, feet (29 percent) 

Other issues

Some people experienced other issues like nearsightedness or a lazy eye, congenital heart disease, and genitourinary issues.

  • 22 out of 61 people had nearsightedness or a lazy eye (33 percent)
  • 8 out of 64 people had congenital heart disease (13 percent)
  • 6 out of 62 people had genitourinary issues (10 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

The content in this guide comes from a published study about KDM6B-related syndrome. Below you can find details about the study, as well as links to summaries or, in some cases, the full article.

  • Politano, D., D’Abrusco, F., Pasca, L., Ferraro, F., Gana, S., Garau, J., Zanaboni, M. P., Rognone, E., Pichiecchio, A., Borgatti, R., Valente, E. M., De Giorgis, V., & Romaniello, R. (2024). Cerebellar heterotopia in an 11-year-old child with KDM6B-related neurodevelopmental disorder: A case report and review of the literature. American journal of medical genetics. Part A, 194(6), e63555. https://pubmed.ncbi.nlm.nih.gov/38326731/
  • Rots, D., Jakub, T. E., Keung, C., Jackson, A., Banka, S., Pfundt, R., de Vries, B. B. A., van Jaarsveld, R. H., Hopman, S. M. J., van Binsbergen, E., Valenzuela, I., Hempel, M., Bierhals, T., Kortüm, F., Lecoquierre, F., Goldenberg, A., Hertz, J. M., Andersen, C. B., Kibæk, M., Prijoles, E. J., … Kleefstra, T. (2023). The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder. American journal of human genetics, 110(6), 963–978. https://pubmed.ncbi.nlm.nih.gov/37196654/

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