NCKAP1-Related Syndrome

Table of contents
- What is NCKAP1-related syndrome?
- Key Role
- Symptoms
- What causes NCKAP1-related syndrome?
- Why does my child have a change in the NCKAP1 gene?
- What are the chances that other family members of future children will have NCKAP1-related syndrome?
- How many people have NCKAP1-related syndrome?
- Do people who have NCKAP1-related syndrome look different?
- How is NCKAP1-related syndrome treated?
- Behavior and development concerns linked to NCKAP1-related syndrome
- Medical and physical concerns linked to NCKAP1-related syndrome
- Where can I find support and resources?
- Sources and References
What is NCKAP1-related syndrome?
NCKAP1-related syndrome happens when there are changes in the NCKAP1 gene. These changes can keep the gene from working as it should.

Key Role
The NCKAP1 gene plays an important role in the structure and organization of cells in the brain.
Symptoms
Because the NCKAP1 gene is important for brain activity, many people who have NCKAP1-related syndrome have:
- Developmental delay
- Intellectual or learning disability
- Autism
- Language issues
- Motor delay
- Anxiety
- Repetitive behaviors
- Aggressive behaviors
- Psychotic episodes
- Sleep challenges
What causes NCKAP1-related syndrome?
NCKAP1-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 NCKAP1 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 NCKAP1 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that NCKAP1-related syndrome is often the result of a de novo variant in NCKAP1. Many parents who have had their genes tested do not have the NCKAP1 genetic variant found in their child who has the syndrome. In some cases, NCKAP1-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
NCKAP1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in v they will likely have symptoms of NCKAP1-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 NCKAP1 gene?
No parent causes their child’s NCKAP1-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 of future children will have NCKAP1-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 NCKAP1-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 NCKAP1-related syndrome, the sibling’s risk of having a child who has NCKAP1-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing NCKAP1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit NCKAP1-related syndrome.

How many people have NCKAP1-related syndrome?
As of 2025, over 25 people with NCKAP1-related syndrome have been identified in medical research.

Do people who have NCKAP1-related syndrome look different?
People who have NCKAP1-related syndrome may look different. People have distinctive facial features, but these features are quite variable.

How is NCKAP1-related syndrome treated?
Scientists and doctors have only just begun to study NCKAP1-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 NCKAP1-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 published articles. It highlights how many people have different symptoms. To learn more about the article, see the Sources and References section of this guide.
Behavior and development concerns linked to NCKAP1-related syndrome
Speech and learning
Most people with NCKAP1-related syndrome had developmental delays or intellectual disabilities, and speech delays or impairment.
- 11 out of 15 people had developmental delays or intellectual disabilities (73 percent)
- 12 out of 17 people had speech delays or impairment (71 percent)

Behavior
People with NCKAP1-related syndrome had behavioral issues, such as autism or features of autism, repetitive behavior, aggressive behavior, attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, obsessive behavior, or self-injury behavior.
- 11 out of 15 people had autism or features of autism (73 percent)
- 9 out of 13 people had repetitive behavior (69 percent)
- 8 out of 14 people had aggressive behavior (57 percent)
- 7 out of 13 people had ADHD (54 percent)
- 4 out of 10 people had anxiety (40 percent)
- 3 out of 13 people had depression (23 percent)
- 3 out of 11people had obsessive behavior (27 percent)
- 1 out of 13 people had self-injury behavior (8 percent)
Brain
Some people with NCKAP1-related syndrome had neurological issues, including brain changes seen on magnetic resonance imaging (MRI), seizures, and either a smaller than average head size (microcephaly) or a larger than average head size (macrocephaly).
- 2 out of 16 people had brain changes seen on MRI (13 percent)
- 7 out of 17 people had seizures (41 percent)
- 1 out of 16 people had microcephaly (6 percent)
- 2 out of 15 people had macrocephaly (13 percent)

Medical and physical concerns linked to NCKAP1-related syndrome
Growth and development
People with NCKAP1-related syndrome had sleep issues, were tall, were overweight, and had skeletal defects. Some people had gastrointestinal issues.
- 9 out of 15 people had sleep issues (60 percent)
- 6 out of 16 people were tall (38 percent)
- 4 out of 16 people were overweight (25 percent)
- 4 out of 12 people had skeletal defects (33 percent)
- 4 out of 16 people had gastrointestinal issues (25 percent)

Vision and hearing
Few people with NCKAP1-related syndrome had visual and hearing impairment.
- 3 out of 12 people had visual impairment (25 percent)
- 2 out of 15 people had hearing impairment (13 percent)

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 NCKAP1: www.simonssearchlight.org/research/what-we-study/NCKAP1
- Simons Searchlight NCKAP1 Facebook community: https://www.facebook.com/groups/nckap1

Sources and References
The content in this guide comes from a published study about NCKAP1-related syndrome. Below you can find details about the study.
- Guo, H., Zhang, Q., Dai, R., Yu, B., Hoekzema, K., Tan, J., Tan, S., Jia, X., Chung, W. K., … & Xia, K. (2020). NCKAP1 disruptive variants lead to a neurodevelopmental disorder with core features of autism. American Journal of Human Genetics, 107(5), 963-976. https://pmc.ncbi.nlm.nih.gov/articles/PMC7674997/