TAOK1-Related Syndrome
What is TAOK1-related syndrome?
TAOK1-related syndrome happens when there are changes to the TAOK1 gene. These changes can keep the gene from working as it should.
Key Role
The TAOK1 gene plays a key role in brain development.
Symptoms
Because the TAOK1 gene is important for brain activity, people who have TAOK1-related syndrome may have:
- Developmental delay
- Intellectual disability
- Motor delays
- Speech and language delay
- Low muscle tone
- Attention-deficit/hyperactivity disorder (ADHD)
- Self-injury behaviors
- Stereotypic repetitive behaviors
- Disruptive behavior
- Gastrointestinal issues
- Brain changes seen on magnetic resonance imaging (MRI)
What causes TAOK1-related syndrome?
TAOK1-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 TAOK1 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 TAOK1 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that TAOK1-related syndrome is often the result of a de novo variant in TAOK1. Many parents who have had their genes tested do not have the TAOK1 genetic variant found in their child who has the syndrome. In some cases, TAOK1-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
TAOK1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in TAOK1 they will likely have symptoms of TAOK1-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 TAOK1 gene?
No parent causes their child’s TAOK1-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 TAOK1-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 TAOK1-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 TAOK1-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 TAOK1-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 TAOK1-related syndrome is 50 percent.
For a person who has TAOK1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have TAOK1-related syndrome?
As of 2026, about 84 people with TAOK1-related syndrome have been identified in a medical clinic. The first case of TAOK1-related syndrome was described in 2019. Scientists expect to find more people who have the syndrome as access to genetic testing improves.
Do people who have TAOK1 related syndrome look different?
People with TAOK1-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:
- Larger than average head size, macrocephaly
- Low muscle tone
- Noticeable forehead
- Downslanted opening of the eyes
- Large tip of the nose
- Long space between the nose and lip
How is TAOK1-related syndrome treated?
Scientists and doctors have only just begun to study TAOK1-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 TAOK1-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 TAOK1-related syndrome
Learning and speech
People with TAOK1-related syndrome had mild to severe developmental delay or intellectual disability and speech and language delay. Some people had typical intellectual development.
- 34 out of 41 people had developmental delay (83 percent)
- 42 out of 48 people had intellectual disability and learning difficulties (88 percent)
- 36 out of 40 people had speech and language delay (90 percent)
Behavior
Some people with TAOK1-related syndrome had behavioral difficulties. A few people had autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), or mental health disorders.
- 15 out of 39 people had behavioral disturbances (38 percent)
- 12 out of 39 people had autism spectrum disorder (31 percent)
- 6 out of 39 people had ADHD (15 percent)
- 6 out of 32 people had mental health disorders (19 percent)
Graphs
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Brain
A few people with TAOK1-related syndrome had seizures, whereas more than one-half of people had lower than average muscle tone (hypotonia).
- 4 out of 50 people had seizures (8 percent)
- 19 out of 32 people had hypotonia (59 percent)
Medical and physical concerns linked to TAOK1-related syndrome
Mobility
Some people with TAOK1-related syndrome had movement issues, including hand stereotypies or joint hypermobility.
- 5 out of 50 people had movement issues (10 percent)
- 11 out of 28 people had joint hypermobility (39 percent)
Feeding and digestion
People with TAOK1-related syndrome had gastrointestinal issues, such as gastroesophageal reflux disease (GERD) and feeding difficulty in the neonatal period. More than one-fourth of people with TAOK1-related syndrome had constipation.
- 4 out of 26 people had GERD (15 percent)
- 10 out of 34 people had neonatal feeding difficulties (29 percent)
- 8 out of 30 people had constipation (27 percent)
Growth
About 1 in 5 people with TAOK1-related syndrome were overweight or obese.
- 7 out of 30 people were overweight or obese (23 percent)
Graphs
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.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on TAOK1: www.simonssearchlight.org/research/what-we-study/taok1
- Simons Searchlight TAOK1 Facebook community: https://www.facebook.com/groups/taok1
Sources and references
- Bowman, P., Grimes, H., Dallosso, A. R., Berry, I., Mullin, S., Rankin, J., & Low, K. J. (2025). Whole genome sequencing for copy number variant detection to improve diagnosis and management of rare diseases. Developmental Medicine & Child Neurology, 67(1), 126-131. doi:10.1111/dmcn.15985
- Elkhateeb, N., Crookes, R., Spiller, M., Pavinato, L., Palermo, F., Brusco, A., Parker, M., Park, S. M., Mendes, A. C., … & Balasubramanian, M. (2025). Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder. Genetics in Medicine, 27(3), 101348. doi:10.1016/j.gim.2024.101348
- Yu, L., Yang, C., Shang, N., Ding, H., Zhu, J., Zhu, Y., Tan, H., & Zhang, Y. (2022). Paternal de novo variant of TAOK1 in a fetus with structural brain abnormalities. Frontiers in Genetics, 13, 836853. doi:10.3389/fgene.2022.836853