GENE GUIDE

TBR1-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 TBR1-Related Syndrome.
a doctor sees a patient

TBR1-related syndrome happens when there are changes in the TBR1 gene. These changes can keep the gene from working as it should.

Key Role

TBR1 plays a key role in the growth of the brain.

Symptoms

Because the TBR1 gene is important for brain activity, many people who have TBR1-related syndrome have:

  • Autism spectrum disorder
  • Speech and language delay
  • Global developmental delay
  • Intellectual disability
  • Delayed walking
  • Delayed speaking or absent speech
  • Brain changes seen on magnetic resonance imaging (MRI)

TBR1-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 TBR1 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 TBR1 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that TBR1-related syndrome is often the result of a de novo variant in TBR1. Many parents who have had their genes tested do not have the TBR1 genetic variant found in their child who has the syndrome. In some cases, TBR1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

TBR1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in TBR1 they will likely have symptoms of TBR1-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 TBR1-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 TBR1-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 TBR1-related syndrome, the sibling’s risk of having a child who has TBR1-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing TBR1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit TBR1-related syndrome. 
  • If one biological parent has the same genetic variant causing TBR1-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 TBR1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 61 people with TBR1-related syndrome have been identified in a medical clinic.

People who have TBR1-related syndrome do not look very different.

Scientists and doctors have only just begun to study TBR1-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 TBR1-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.

Learning

People with TBR1-related syndrome had global developmental delay or intellectual disabilities, ranging from mild to severe.

  • 39 out of 39 people had global developmental delay or intellectual disability (100 percent)

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

  • 3 out of 38 people had mild ID (8 percent)
  • 10 out of 38 people had moderate ID (26 percent)
  • 23 out of 38 people had severe ID (61 percent)
8%
3 out of 38 people had mild ID.
26%
10 out of 38 people had moderate ID.
61%
23 out of 38 people had severe ID.

Behavior

People with TBR1-related syndrome had behavioral issues, such as features of autism, attention-deficit/hyperactivity disorder (ADHD), or aggression.

  • 29 out of 34 people had behavioral disorders other than autism (85 percent)
  • 30 out of 39 people had features of autism (76 percent)

Brain

People with TBR1-related syndrome had seizures, lower than average muscle tone (hypotonia), abnormal movements, and a smaller than average head size (microcephaly). A few people had subtle brain changes seen on magnetic resonance imaging (MRI).

  • 7 out of 36 people had seizures (19 percent)
  • 18 out of 35 people had hypotonia (51 percent)
  • 5 out of 31 people had microcephaly (16 percent)
  • 7 out of 35 people had abnormal movements (20 percent)
Human head showing brain outline
19%
7 out of 36 people had seizures.
51%
18 out of 35 people had hypotonia.
16%
5 out of 31 people had microcephaly.
20%
7 out of 35 people had abnormal movements.

Feeding and digestion

People with TBR1-related syndrome had gastrointestinal issues, such as feeding difficulties and constipation. Some people had severe feeding difficulties and needed a feeding tube.

  • 6 out of 34 people had feeding difficulties (18 percent)
  • 8 out of 31 people had structural findings (26 percent)

Skeletal findings

People with TBR1-related syndrome were sometimes shorter than average and had skeletal defects. Skeletal findings included relaxed joints, flat feet (pes planus), and a sideways curve of the spine (scoliosis).

  • 6 out of 28 people were shorter than average (21 percent)
  • 18 out of 32 people had skeletal defects (56 percent)
21%
6 out of 28 people were shorter than average.
56%
18 out of 32 people had skeletal defects.

Where can I find support and resources?

TBR1 Syndrome Website: https://www.tbr1syndrome.com/

TBR1 Genetic Mutations Facebook Group: https://www.facebook.com/groups/508232163293215/

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 TBR1-related syndrome.

  • Liu, J., Zhang, J., Shen, Y., Li, Y., Luo, H., & Gan, J. (2024). Analysis of a child featuring global developmental delay and autism due to variant of TBR1 gene and a literature review [Abstract in English, Article in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 41(3), 335-338. https://pubmed.ncbi.nlm.nih.gov/38448025/
  • Nambot, S., Faivre, L., Mirzaa, G., Thevenon, J., Bruel, A. L., Mosca-Boidron, A. L., Masurel-Paulet, A., Goldenberg, A., Le Meur, N., … & Thauvin-Robinet, C. (2020). De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: Report of 25 new individuals and review of the literature. European Journal of Human Genetics, 28(6), 770-782. https://pubmed.ncbi.nlm.nih.gov/32005960/

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