GENE GUIDE

CTNNB1-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 CTNNB1-Related Syndrome.
a doctor sees a patient

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

Many people who have CTNNB1-related syndrome have:

  • Intellectual disability
  • Developmental delay
  • Speech delay
  • Motor delay
  • Behavioral challenges, such as autism, aggression, attention deficit hyperactivity disorder, also called ADHD
  • Sleep difficulty
  • Movement issues, including cerebral palsy
  • Feeding challenges
  • Retinal issues such as fewer blood vessels, holes, scarring, and retinal detachment that may lead to vision impairment. A common finding may be called familial exudative vitreoretinopathy (FEVR)
  • Less common features that may be associated with CTNNB1 genetic variants include heart defects and exaggerated startle response

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, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the gene change.

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because CTNNB1 plays a key role in cell communication, de novo changes in this gene can have a meaningful effect.

Research shows that CTNNB1-related syndrome is often the result of a de novo change in CTNNB1. Many parents who have had their genes tested do not have the CTNNB1 gene change found in their child who has the syndrome. In some cases, CTNNB1-related syndrome happens because the gene change was passed down from a parent. This is called dominant inheritance.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change.

Child who has genetic change in CTNNB1 gene

Genetic change occurs in egg or sperm after fertilization
Child with de novo genetic change in autism gene

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.

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 birth parents.

    • If neither birth parent has the same gene change 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 change in the gene.
    • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has CTNNB1-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

    • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has CTNNB1-related syndrome.
    • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has CTNNB1-related syndrome 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.

As of 2019, about 20 people in the world with changes in the CTNNB1 gene had been described in the medical research. The first case of CTNNB1-related syndrome was described in 2012. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have CTNNB1-related syndrome can look a little different from others. Appearance can vary and can include some but not all of these features:

  • Thin upper lip
  • Wide-spaced teeth
  • Large nose
  • Fair, thin hair and fair skin

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:

    • 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 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.

Learning

Learning issues are common.

Behavior

Autism and other behavior concerns are common. Many people have poor sleep.

Speech

Almost everyone has speech delay.

Muscle tone

Low muscle tone was very common.

  • 9 out of 10 people have low muscle tone.

Motor concerns

Motor delays are very common.

Growth

Many people had a small head.

  • 12 out of 16 people had a small head.
90%
9 out of 10 people have low muscle tone.
75%
12 out of 16 people had a small head.

Where can I find support and resources?

Simons Searchlight is another research program sponsored and run by the Simons Foundation Autism Research Initiative, also known as SFARI. As part of the next step in your research journey, Simons Searchlight offers you the opportunity to partner with scientists and other families who have the same gene change. Simons Searchlight is a registry for more than 200 genetic changes that are associated with neurodevelopmental conditions, including autism spectrum disorder. Simons Searchlight makes it easier for researchers to access the information they need to advance research on a condition. To register for Simons Searchlight,  click “Join Us” at the top of this page.

Other resources:

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

Simons Searchlight CTNNB1 Facebook community

CTNNB1 Foundation Website

www.CTNNB1.org

Cure CTNNB1

www.CURECTNNB1.org

Sources and references

The content in this guide comes from published studies about CTNNB1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Kuechler A. et al. Human Genetics, 134, 97-109, (2015). De novo mutations in beta-catenin (CTNNB1) appear to be a frequent cause of intellectual disability: Expanding the mutational and clinical spectrum www.ncbi.nlm.nih.gov/pubmed/25326669
  • Kharbanda M. et al. European Journal of Medical Genetics, 60, 130-135, (2017). Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals www.ncbi.nlm.nih.gov/pubmed/27915094

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