RALGAPB-Related Syndrome
What is RALGAPB-related syndrome?
RALGAPB-related syndrome happens when there are changes in the RALGAPB gene. These changes can keep the gene from working as it should.
Key Role
Changes in the RALGAPB gene are linked to intellectual disability and autism.
Symptoms
Because the RALGAPB gene may be important for brain activity, people who have RALGAPB-related syndrome may have:
- Developmental delay
- Autism spectrum disorder
- Seizures
- Speech delay
What causes RALGAPB-related syndrome?
RALGAPB-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 RALGAPB 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 RALGAPB plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that RALGAPB-related syndrome is often the result of a de novo variant in RALGAPB. Many parents who have had their genes tested do not have the RALGAPB genetic variant found in their child who has the syndrome. In some cases, RALGAPB-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
RALGAPB-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in RALGAPB they will likely have symptoms of RALGAPB-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.
Children have a 50% chance of inheriting the genetic change.
Autosomal Dominant Genetic Syndrome
Why does my child have a change in the RALGAPB gene?
No parent causes their child’s changes in RALGAPB. 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.
What are the chances that other family members or future children will have RALGAPB-related syndrome?
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 RALGAPB-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 RALGAPB-related syndrome, the sibling’s risk of having a child who has RALGAPB-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing RALGAPB-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit RALGAPB-related syndrome.
- If one biological parent has the same genetic variant causing RALGAPB-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 RALGAPB-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have RALGAPB-related syndrome?
As of 2026, about 15 people with RALGAPB-related syndrome have been described in medical research. The first case of this condition was described in 2013. Scientists expect to find more people who have the syndrome as access to genetic testing improves.
Do people who have RALGAPB-related syndrome look different?
People who have RALGAPB-related syndrome might not look very different. It is unknown at this time if there are any changes in appearance.
How are people who have changes in RALGAPB treated?
Scientists and doctors have only just begun to study people who have changes in the RALGAPB gene. At this point, there are no medicines designed to treat the condition. 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
- Developmental 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 people who have autism begin as early as possible, ideally before a child begins school.
If seizures happen, consult a neurologist. There are many different 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/what-is-epilepsy/seizure-types.
A doctor may also refer people to other specialists as needed.
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.
Behavior and development concerns linked to RALGAPB-related syndrome
Most people with RALGAPB-related syndrome were identified from large-scale genetic sequencing studies. Usually, researchers do not have as many medical details on the participants in these studies. Some of the medical features reported for people with RALGAPB-related syndrome were developmental delay, autism, seizures, speech delay, and aggression.
In mid 2026, the Simons Searchlight registry had six people with RALGAPB-related syndrome, and only two participants had provided medical history. As more people register and share medical information, we will be able to provide more information to the RALGAPB community.
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
- Shah, A. A., Zhang, G., Li, K., Liu, C., Kanhar, A. A., Wang, M., Quan, Y., Wu, H., Shen, L., … & Guo, H. (2020). Excess of RALGAPB de novo variants in neurodevelopmental disorders. European Journal of Medical Genetics, 63(11), 104041. doi:10.1016/j.ejmg.2020.104041
- Zhou, X., Feliciano, P., Shu, C., Wang, T., Astrovskaya, I., Hall, J. B., Obiajulu, J. U., Wright, J. R., Murali, S. C., … & Chung, W. K. (2022). Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nature Genetics, 54(9), 1305-1319. doi:10.1038/s41588-022-01148-2