GENE GUIDE

RORB-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 2025. 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 RORB-Related Syndrome.
a doctor sees a patient

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

The RORB gene is located on chromosome 9, in a region called 9q21. Chromosomes are structures in our cells that house our genes.

Some people are missing a piece of chromosome 9q21 that includes the RORB gene and have what is called 9q21-related syndrome. Others have a small change within the RORB gene itself. People with these syndromes have similar symptoms.

Key Role

The RORB gene plays a key role in the growth of different types of brain cells.

Symptoms

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

  • Developmental delay, or intellectual disability, or both
  • Autism or features of autism
  • Seizures
  • Speech issues
  • Aggression
  • Sensitivity to light

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

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

Autosomal dominant conditions

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

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

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

As of 2024, at least 50 people with RORB-related syndrome have been identified in a medical clinic.

People who have RORB-related syndrome might not look very different.

Scientists and doctors have only just begun to study RORB-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 RORB-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 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 have been looking for links between the type of RORB genetic variant and the specific medical features that a person develops. Currently, there is no clear link between the genetic variant and medical features.

Learning

The majority of people with RORB-related syndrome had global developmental delay or intellectual disabilities, ranging from mild to severe. People had speech delays.

  • 29 out of 34 people had global developmental delay or intellectual disability (85 percent)

The severity of intellectual disability (ID) varied among people:

  • 15 out of 29 people had mild ID (52 percent)
  • 13 out of 29 people had moderate ID (45 percent)
  • 1 out of 29 people had severe ID (4 percent)
52%
15 out of 29 people had mild ID.
45%
13 out of 29 people had moderate ID.
4%
1 out of 29 people had severe ID.

Behavior

People with RORB-related syndrome had behavioral issues, such as autism, attention-deficit/hyperactivity disorder (ADHD), aggression, anxiety, and mood disorders.

  • 9 out of 35 people had autism spectrum disorder or features of autism (26 percent)
  • 9 out of 35 people had ADHD (26 percent)
  • 7 out of 35 people had anxiety (20 percent)
  • 4 out of 35 people had aggression (11 percent)
  • 2 out of 35 people had mood disorders (6 percent)
26%
9 out of 35 people had autism spectrum disorder or features of autism.
26%
9 out of 35 people had ADHD.
20%
7 out of 35 people had anxiety.
11%
4 out of 35 people had aggression.
6%
2 out of 35 people had mood disorders.

Brain

Most people with RORB-related syndrome had seizures. The average age of onset was 3 years, with the earliest age of onset from 3 months to 12 years. The most common seizure type was absence seizures. Many people were seizure-free with treatment. About 1 in 4 people had sleeping difficulties.

  • 31 out of 35 people had seizures (89 percent)
  • 25 out of 31 people had absence seizures (81 percent)
  • 13 out of 19 people were seizure-free with treatment (68 percent)
  • 8 out of 35 people had sleeping difficulties (23 percent)
Human head showing brain outline

Movement

Few people with RORB-related syndrome had a lower than average muscle tone (hypotonia), poor coordination, and/or poor muscle control (ataxia).

  • 4 out of 35 people had hypotonia (11 percent)
  • 2 out of 35 people had poor coordination (6 percent)
  • 1 out of 35 people had ataxia (3 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 published studies about RORB-related syndrome.

  • Gokce-Samar, Z., Vetro, A., De Bellescize, J., Pisano, T., Monteiro, L., Penaud, N., Korff, C. M., Fluss, J., Marini, C., … & Lesca, G. (2024). Molecular and phenotypic characterization of the RORB-related disorder. Neurology, 102(2), e207945. https://pubmed.ncbi.nlm.nih.gov/38165337/

Stay connected with Simons Searchlight

Join our newsletter to receive updates