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GENE GUIDE

NAA15-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 NAA15-Related Syndrome.
a doctor sees a patient

NAA15-related syndrome is also called NAA15-related neurodevelopmental syndrome or intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities. For this webpage, we will be using the name NAA15-related syndrome to encompass the wide range of variants observed in the people identified.

NAA15-related syndrome happens when there are changes to the NAA15 gene. These changes can keep the gene from working as it should.

Key Role

The NAA15 gene plays a key role in development. It makes chemical changes to molecules in cells known as proteins. These changes are important for cells to function properly.

Symptoms

Because the NAA15 gene is important for brain activity, many people who have NAA15-related syndrome have:

  • Developmental delay
  • Intellectual disability, mild to severe
  • Speech impairment
  • Behavior issues, including autism
  • Heart issues
  • Seizures
  • Visual issues that are caused by parts of the brain that control vision
  • Low muscle tone
  • Sleep issues
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Feeding issues
  • Hearing loss

NAA15-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 NAA15 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 NAA15 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that NAA15-related syndrome is often the result of a de novo variant in NAA15. Many parents who have had their genes tested do not have the NAA15 genetic variant found in their child who has the syndrome. In some cases, NAA15-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

NAA15-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in NAA15 they will likely have symptoms of NAA15-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 NAA15 gene?

No parent causes their child’s NAA15-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 NAA15-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 NAA15-related syndrome, the sibling’s risk of having a child who has NAA15-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing NAA15-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit NAA15-related syndrome. 
  • If one biological parent has the same genetic variant causing NAA15-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 NAA15-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, about 180 people in the world with NAA15-related syndrome have been identified in a medical clinic.

People who have NAA15-related syndrome might not look very different. Some people have been described to have unique facial features, but there is no common pattern.

Scientists and doctors have only just begun to study NAA15-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 NAA15-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 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 and speech

People with NAA15-related syndrome had developmental delay or intellectual disability and speech and language delay. Developmental patterns based on scores from the Vineland Adaptive Behavior-3 survey were also universally delayed. The Vineland assesses four main behavioral domains: communication, daily living skills, socialization, and motor.

  • 14 out of 44 people had developmental delay (32 percent)
  • 28 out of 30 people had intellectual disability (93 percent)
  • 37 out of 40 people had speech delay (93 percent)

Behavior

Many people with NAA15-related syndrome had behavioral issues, such as autism or features of autism and attention-deficit/hyperactivity disorder (ADHD).

  • 37 out of 45 people had behavioral issues (83 percent)
  • 16 out of 48 people had ADHD (33 percent)

 

83%
37 out of 45 people had behavioral issues.
33%
16 out of 48 people had ADHD.

Brain

People with NAA15-related syndrome had seizures, lower than average muscle tone (hypotonia), and brain changes seen on magnetic resonance imaging (MRI).

  • 11 out of 36 people had seizures (31 percent)
  • 10 out of 27 people had hypotonia (37 percent)
  • 5 out of 23 people had brain changes on MRI (22 percent)
Human head showing brain outline
31%
11 out of 36 people had seizures.
35%
10 out of 27 people had hypotonia.
22%
5 out of 23 people had brain changes on MRI.

Vision

Eye issues included, but were not limited to, farsightedness (hyperopia), crossed eyes (strabismus), nearsightedness (myopia), uncontrolled eye movements (nystagmus), an imperfection of the eye that causes blurred distance and near vision (astigmatism), and depth perception issues.

Heart

About one out of five people with NAA15-related syndrome had heart issues, including a thickening and stiffening of the heart wall (hypertrophic cardiomyopathy), an abnormal heart rhythm (arrhythmia), and high blood pressure (hypertension).

  • 5 out of 23 people had heart issues (22 percent)

Other features

Some people with NAA15-related syndrome had hearing loss, skeletal or connective tissue defects, or feeding difficulties.

  • 11 out of 26 people had skeletal or connective tissue defects (42 percent)
  • 9 out of 19 people had feeding difficulties (47 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.”

Sources and references

  • Christ, C., Makwana, R., Appah, F. S. K., Cheng, H., Moreno, C., Marchi, E., Harpell, R., & Lyon, G. J. (2026). Letter: Psychosis following hormonal therapy in NAA15-related neurodevelopmental disorder. Journal of Child and Adolescent Psychopharmacology, 36(7), 454-456. doi:10.1177/10445463261462385
  • Makwana, R., Christ, C., Patel, R., Marchi, E., Harpell, R., & Lyon, G. J. (2025). Natural history of NAA15-related neurodevelopmental disorder through adolescence. American Journal of Medical Genetics Part A, 197(6), e64009. doi:10.1002/ajmg.a.64009
  • Patel, R., Park, A. Y., Marchi, E., Gropman, A. L., Whitehead, M. T., & Lyon, G. J. (2024). Ophthalmic manifestations of NAA10-related and NAA15-related neurodevelopmental syndromes: Analysis of cortical visual impairment and refractive errors. American Journal of Medical Genetics Part A, 194(12), e63821. doi:10.1002/ajmg.a.63821
  • Patel, R., Makwana, R., Christ, C., Marchi, E., Miyake, C. Y., Goncalves, F. G., Lyon, G. J., & Whitehead, M. T. (2025). Neuroanatomical features of NAA10 and NAA15-related neurodevelopmental syndromes. Journal of Neuroradiology, 52(4), 101339. doi:10.1016/j.neurad.2025.101339
  • Ritter, A., Berger, J. H., Deardorff, M., Izumi, K., Lin, K. Y., Medne, L., & Ahrens-Nicklas, R. C. (2021). Variants in NAA15 cause pediatric hypertrophic cardiomyopathy. American Journal of Medical Genetics Part A, 185(1), 228-233. doi:10.1002/ajmg.a.61928
  • Tian, Y., Xie, H., Yang, S., Shangguan, S., Wang, J., Jin, C., Zhang, Y., Cui, X., Lyu, Y., … & Wang, L. (2022). Possible catch-up developmental trajectories for children with mild developmental delay caused by NAA15 pathogenic variants. Genes (Basel), 13(3), 536. doi:10.3390/genes13030536

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