CTNNB1-Related Syndrome
CTNNB1-related syndrome is also called CTNNB1 neurodevelopmental disorder. For this webpage, we will be using the name CTNNB1-related syndrome to encompass the wide range of variants observed in the people identified.
What is CTNNB1-related syndrome?
CTNNB1-related syndrome happens when there are changes to the CTNNB1 gene. These changes can keep the gene from working as it should.
Key Role
The CTNNB1 gene plays a key role in the communication that happens between cells and how cells connect to each other.
Symptoms
Because the CTNNB1 gene is important for brain activity, many people who have CTNNB1-related syndrome have:
- Developmental delay
- Intellectual disability
- Speech delay
- Behavioral challenges, such as autism, aggression, attention-deficit/hyperactivity disorder (ADHD)
- Aggression
- Sleep difficulty
- Movement issues, including cerebral palsy
- Feeding challenges
- Low muscle tone
- Small head size
- Sideways curve of the spine, also called scoliosis
- Retinal issues, such as fewer blood vessels, holes, scarring, and retinal detachment that may lead to vision impairment; A common finding may be familial exudative vitreoretinopathy (FEVR)
- Less common features that may be associated with CTNNB1 genetic variants include heart defects and an exaggerated startle response
What causes CTNNB1-related syndrome?
CTNNB1-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 CTNNB1 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 CTNNB1 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that CTNNB1-related syndrome is often the result of a de novo variant in CTNNB1. Many parents who have had their genes tested do not have the CTNNB1 genetic variant found in their child who has the syndrome. In some cases, CTNNB1-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
CTNNB1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CTNNB1 they will likely have symptoms of CTNNB1-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
Why does my child have a change in the CTNNB1 gene?
No parent causes their child’s CTNNB1-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.
What are the chances that other family members or future children will have CTNNB1-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 CTNNB1-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 CTNNB1-related syndrome, the sibling’s risk of having a child who has CTNNB1-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing CTNNB1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CTNNB1-related syndrome.
- If one biological parent has the same genetic variant causing CTNNB1-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 CTNNB1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have CTNNB1-related syndrome?
As of 2026, more than 250 people with CTNNB1-related syndrome have been identified in a medical clinic.
Do people who have CTNNB1-related syndrome look different?
People with CTNNB1-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:
- Larger tip of the nose
- Small nostrils
- Thin upper lip
- Thin, fair, or sparse hair
- Long distance from the base of the nose and upper lip
- Smaller than average head size
- Ear defects
How is CTNNB1-related syndrome treated?
Scientists and doctors have only just begun to study CTNNB1-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:
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- 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:
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- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for CTNNB1-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 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 CTNNB1-related syndrome
Learning and speech
All people with CTNNB1-related syndrome had developmental delay, or mild to severe intellectual disability, and most had speech and language delay. Some adults with CTNNB1-related syndrome were able to care for themselves and raise children with support. The age at which first words were spoken ranged from 12 months to 14 years. People were able to speak in sentences between ages 6 and 14 years old. Some people were nonverbal.
- 113 out of 113 people had developmental delay and or intellectual disability (100 percent)
- 67 out of 73 people had speech and language delay (92 percent)
Behavior
People with CTNNB1-related syndrome had behavioral issues, such as autism or features of autism, hyperactivity, attention-deficit/hyperactivity disorder (ADHD), aggression, difficulty sleeping, emotional dysregulation, and anxiety.
- 22 out of 65 people had autism or features of autism (34 percent)
- 20 out of 66 people had hyperactivity or ADHD (30 percent)
- 18 out of 37 people had aggression (49 percent)
- 39 out of 71 people had difficulty sleeping (55 percent)
- 21 out of 49 people had anxiety (43 percent)
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Brain
People with CTNNB1-related syndrome had lower than average muscle tone (hypotonia), a smaller than average head size (microcephaly), and movement issues, such as dystonia or ataxia. Lower body hypertonia, high muscle tone, a diagnosis of cerebral palsy, and having an exaggerated startle response were common. Brain changes seen on magnetic resonance imaging (MRI) included nonspecific white matter defects and hypoplasia of the frontal lobes.
- 39 out of 47 people had hypotonia (83 percent)
- 82 out of 108 people had microcephaly (76 percent)
- 51 out of 98 people had dystonia (52 percent)
- 16 out of 38 people had ataxia (42 percent)
- 22 out of 25 people had lower body hypertonia (88 percent)
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Medical and physical concerns linked to CTNNB1-related syndrome
Vision
People with CTNNB1-related syndrome had vision impairment and eye issues, such as familial exudative vitreoretinopathy (FEVR), crossed eyes (strabismus), nearsightedness (myopia), and an imperfection of the eye that causes blurred distance and near vision (astigmatism). A few people were legally blind.
- 96 out of 107 people had vision issues (90 percent)
- 13 out of 40 people had FEVR (33 percent)
- 51 out of 81 people had strabismus (63 percent)
- 15 out of 56 people had other vision problems (27 percent)
Development
Some people with CTNNB1-related syndrome had changes in development, including intrauterine growth restriction, short height, and a sideways curve of the spine, also called scoliosis.
- 10 out of 44 people had intrauterine growth restriction (23 percent)
- 8 out of 39 people had short height (21 percent)
- 6 out of 30 people had scoliosis (20 percent)
Tumors
You may have seen reports of people with cancer having genetic variations in the CTNNB1 gene. In general, genetic variants that are linked to CTNNB1-related syndrome are different from genetic variants that are associated with cancer. Genetic variants that are linked to CTNNB1-related syndrome do not increase the risk of cancer in a person.
Where can I find support and resources?
CTNNB1 Connect and Cure
CTNNB1 Connect and Cure is a nonprofit organization dedicated to finding treatment options and a cure for CTNNB1 Syndrome while improving the lives of our patients and community.
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.”
- Learn more about Simons Searchlight – www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on CTNNB1 –www.simonssearchlight.org/research/what-we-study/ctnnb1
- Simons Searchlight CTNNB1 Facebook community – https://www.facebook.com/groups/CTNNB1
Sources and references
- Chauvet-Piat, E., François-Heude, M. C., Manes, G., Coget, A., Leboucq, N., Lecardonnel, B., Baide-Mairena, H., Allais, M., Touati, S., … & Roubertie, A. (2026). CTNNB1-related disorders: Clinical and radiological contributions from a French cohort. Frontiers in Neurology, 17, 1754143. doi:10.3389/fneur.2026.1754143
- Ho, S. K. L., Tsang, M. H. Y., Lee, M., Cheng, S. S. W., Luk, H., Lo, I, F. M., & Chung, B. H. Y. CTNNB1 neurodevelopmental disorder. 2022 May 19. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580527/
- Lee, J., Yoo, J., Lee, S., & Jang, D. H. (2023). CTNNB1-related neurodevelopmental disorder mimics cerebral palsy: Case report. Frontiers in Pediatrics, 11, 1201080. doi:10.3389/fped.2023.1201080
- Yan, D., Sun, Y., Xu, N., Yu, Y., Zhan, Y., & Mainland Chinese League of NEDSDV Rare Disease. (2022). Genetic and clinical characteristics of 24 mainland Chinese patients with CTNNB1 loss-of-function variants. Molecular Genetics & Genomic Medicine, 10(11), e2067. doi:10.1002/mgg3.2067