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 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 NAA15-Related Syndrome.
a doctor sees a patient

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 in the development, many people who have NAA15-related neurodevelopmental syndrome have:

  • Motor delays
  • Developmental delay
  • Intellectual disability, mild to severe 
  • Speech impairment
  • Behavior issues, including autism
  • Cardiac issues
  • Seizures
  • Visual issues that are caused by parts of the brain that control vision

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

Research shows that NAA15-related syndrome is often the result of a de novo change in NAA15. Many parents who have had their genes tested do not have the NAA15 gene change found in their child who has the syndrome. In some cases, NAA15-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 NAA15 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 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 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 NAA15-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 NAA15-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 NAA15-related syndrome 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 2023, about 66 people in the world with NAA15-related neurodevelopmental syndrome have been described in medical research. The first case of NAA15related syndrome was described in 2018. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have NAA15-related syndrome do not look very different.

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

Intellectual disability is common among people who have NAA15-related syndrome.

  • 23 out of 23 people have an intellectual disability.

Speech

Many people have speech delay.

  • 32 out of 33 people have speech delay.

Behavior

Many people have behavior issues, including autism and attention deficit hyperactivity disorder, also called ADHD.

  • 30 out of 33 people have behavior issues.

 

100%
23 out of 23 people have an intellectual disability.
97%
32 out of 33 people have speech delay.
91%
30 out of 33 people have behavior issues.

Sitting and walking

Almost everyone who has NAA15-related syndrome has motor delay.

  • 31 out of 32 people have motor delay.

Muscle tone

More than one-third have low muscle tone.

  • 7 out of 18 people have low muscle tone.

Brain

About one-quarter have seizures.

  • 6 out of 23 people have seizures.
94%
31 out of 32 people have motor delay.
39%
7 out of 18 people have low muscle tone. 
23%
6 out of 23 people have seizures.

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 published studies about NAA15-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Cheng H. et al. American Journal of Human Genetics, 102, 985-994, (2018). Truncating variants in NAA15 are associated with variable levels of intellectual disability, autism spectrum disorder, and congenital anomalies www.ncbi.nlm.nih.gov/pubmed/29656860
  • Cheng H. et al. Human Molecular Genetics, 28, 2900-2919, (2019). Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15 www.ncbi.nlm.nih.gov/pubmed/31127942

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