GENE GUIDE

BRSK2-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 BRSK2-Related Syndrome.
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BRSK2-related syndrome happens when there are changes to the BRSK2 gene. These changes can keep the gene from working as it should.

Key Role

The BRSK2 gene plays a key role in brain development.

Symptoms

Because the BRSK2 gene is important in the development and function of brain cells, many people who have BRSK2-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Autism
  • Motor delay
  • Sleep issues
  • Feeding issues
  • Seizures

BRSK2-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 BRSK2 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 BRSK2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that BRSK2-related syndrome is often the result of a de novo variant in BRSK2. Many parents who have had their genes tested do not have the BRSK2 genetic variant found in their child who has the syndrome. In some cases, BRSK2-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

BRSK2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in BRSK2 they will likely have symptoms of BRSK2-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 BRSK2 gene?

No parent causes their child’s BRSK2-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 BRSK2-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 BRSK2-related syndrome, the sibling’s risk of having a child who has BRSK2-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing BRSK2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit BRSK2-related syndrome. 
  • If one biological parent has the same genetic variant causing BRSK2-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 BRSK2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 19 people with BRSK2-related syndrome have been described in the medical literature. The first case of BRSK2-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 BRSK2-related syndrome might not look very different. Some people have been described to have unique facial features, but there is no common pattern.

Scientists and doctors have only just begun to study BRSK2-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 BRSK2-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 nine people who have the syndrome. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Behavior

Most people with BRSK2-related syndrome have an autism diagnosis.

  • 17 out of 18 people have an autism diagnosis (94 percent).

Speech

Most people with BRSK2-related syndrome have speech delays.

  • 17 out of 18 have speech delays (94 percent).

Learning

Most people have intellectual disability, from mild to severe.

  • 14 out of 18 have mild to severe intellectual disability (78 percent).
94%
17 out of 18 people have an autism diagnosis.
94%
17 out of 18 people have speech delays.
78%
14 out of 18 have mild to severe intellectual disability.

Motor concerns

Most people have motor issues.

  • 12 out of 16 have motor issues (75 percent).

Where can I find support and resources?

At this time, we are not aware of support groups for families with changes in BRSK2. More families who have changes in BRSK2 will likely be found in the future.

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 BRSK2-related syndrome. Below you can find details about the study, as well as a link to a summary.

  • Bacchelli E, Viggiano M, Ceroni F, et al. Whole genome analysis of rare deleterious variants adds further evidence to BRSK2 and other risk genes in Autism Spectrum Disorder. Preprint. Res Sq. 2023;rs.3.rs-3468592. Published 2023 Oct 28. doi:10.21203/rs.3.rs-3468592/v1
  • Hiatt SM. et al. American Journal of Human Genetics, 104, 701-708, (2019). Deleterious variation in BRSK2 associates with a neurodevelopmental disorder www.ncbi.nlm.nih.gov/pubmed/30879638
  • Hu Y, Li M, Shen Y, et al. Case report: A novel frameshift mutation in BRSK2 causes autism in a 16-year old Chinese boy. Front Psychiatry. 2023;14:1205204. Published 2023 Aug 21. doi:10.3389/fpsyt.2023.1205204

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