GENE GUIDE

TANC2-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 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 TANC2-Related Syndrome.
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TANC2-related syndrome happens when there are changes to the TANC2 gene. These changes can keep the gene from working as it should.

Key Role

The TANC2 gene helps to control the connections between brain cells.

Symptoms

Because the TANC2 gene is important for brain activity, many people who have TANC2-related syndrome have:

  • Autism
  • Intellectual disability
  • Delayed speaking or inability to speak
  • Delayed motor development
  • Uncoordinated movements
  • Seizures
  • Aggression 
  • Gastrointestinal issues
  • A sideways curve of the spine, also called scoliosis

TANC2-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 TANC2 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 TANC2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that TANC2-related syndrome is often the result of a de novo variant in TANC2. Many parents who have had their genes tested do not have the TANC2 genetic variant found in their child who has the syndrome. In some cases, TANC2-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

TANC2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in TANC2 they will likely have symptoms of TANC2-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

Why does my child have a change in the TANC2 gene?

No parent causes their child’s TANC2-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 TANC2-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 TANC2-related syndrome, the sibling’s risk of having a child who has TANC2-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing TANC2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit TANC2-related syndrome. 
  • If one biological parent has the same genetic variant causing TANC2-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 TANC2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 33 people with TANC2-related syndrome have been identified in a medical clinic.

People who have TANC2-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Smaller than average head size, also called microcephaly
  • Widely spaced teeth
  • Deep-set eyes
  • Crossed eyes, also called strabismus
  • Large nose and mouth

Scientists and doctors have only just begun to study TANC2-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 TANC2-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 a major published article. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide

Speech and learning

The majority of people with TANC2-related syndrome had developmental delay and or intellectual disabilities, and speech delay.

  • 21 out of 22 people had global developmental delay or intellectual disability (96 percent)
  • 20 out of 22 people had speech delay (91 percent)

Behavior

People with TANC2-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), aggression, repetitive behaviors, anxiety, or psychiatric issues.

  • 15 out of 21 people had autism or features of autism (71 percent)
  • 4 out of 14 people had ADHD (29 percent)
  • 6 out of 16 people had aggression (38 percent)
  • 13 out of 19 people had repetitive behaviors (68 percent)
  • 4 out of 13 people had anxiety (31 percent)
  • 3 out of 15 people had psychiatric issues (20 percent)

Brain

Some people with TANC2-related syndrome had seizures, lower than average muscle tone (hypotonia), a smaller than average head size (microcephaly), or brain changes seen on magnetic resonance imaging (MRI). Three children had developmental regression.

  • 12 out of 22 people had seizures (55 percent)
  • 5 out of 15 people had hypotonia (33 percent)
  • 8 out of 15 people had microcephaly (53 percent)
  • 3 out of 18 people had brain changes seen on MRI (17 percent)
55%
12 out of 22 people had seizures.
33%
5 out of 15 people had hypotonia.
53%
8 out of 15 people had microcephaly.
17%
3 out of 18 people had brain changes seen on MRI.

Feeding and digestion

People with TANC2-related syndrome had gastrointestinal issues, such as chronic constipation.

  • 9 out of 16 people had chronic constipation (56 percent)

Skeletal findings

People with TANC2-related syndrome had skeletal defects. Skeletal findings included relaxed joints and defects of the spinal column, feet, or chest.

  • 3 out of 9 people had relaxed joints (33 percent)
  • 5 out of 14 people had a defect of the spinal column (36 percent)
  • 5 out of 15 people had defects of the feet (33 percent)
  • 4 out of 13 people had a defect of the chest (31 percent)
33%
3 out of 9 people had relaxed joints.
36%
5 out of 14 people had a defect of the spinal column.
33%
5 out of 15 people had defects of the feet.
31%
4 out of 13 people had a defect of the chest.

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 a published study about TANC2-related syndrome.

  • Guo, H., Bettella, E., Marcogliese, P. C., Zhao, R., Andrews, J. C., Nowakowski, T. J., Gillentine, M. A., Hoekzema, K., Wang, T., … & Eichler, E. E. (2019). Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. Nature Communications, 10(1), 4679. https://pubmed.ncbi.nlm.nih.gov/31616000/
  • Tassano, E., Accogli, A., Ronchetto, P., Tortora, D., Tavella, E., Gimelli, G., Mancardi, M., Malacarne, M., & Coviello, D. A. (2020). 17q23.3 de novo microdeletion involving only TANC2 gene: A new case. European Journal of Medical Genetics, 63(12), 104094. https://pubmed.ncbi.nlm.nih.gov/33160097/
  • Tian, Y., Shi, Z., Hou, C., Li, W., Wang, X., Zhu, H., Li, X., & Chen, W. X. (2021). Truncating mutation in TANC2 in a Chinese boy associated with Lennox-Gastaut syndrome: A case report. BMC Pediatrics, 21(1), 546. https://pubmed.ncbi.nlm.nih.gov/34861844/

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