GENE GUIDE

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

NBEA-related syndrome is also called NBEA-related neurodevelopmental disorder. For this webpage, we will be using the name NBEA-related syndrome to encompass the wide range of variants observed in the people identified.

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

Key Role

The NBEA gene plays a key role in the communication that happens between brain cells.

Symptoms

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

  • Developmental delay
  • Intellectual disability
  • Autism
  • Seizures
  • Small head size
  • Behavioral issues, such as aggression and attention-deficit/hyperactivity disorder (ADHD)

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

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

Autosomal dominant conditions

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

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

  • If neither parent has the same genetic variant causing NBEA-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit NBEA-related syndrome.

As of 2024, at least 53 people with NBEA-related syndrome have been identified in a medical clinic. The first case of NBEA-related syndrome was described in 2003. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have NBEA-related syndrome may not look that different. Some people have a smaller than average head size.

Scientists and doctors have only just begun to study NBEA-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 NBEA-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 describing people who have the syndrome. To learn more about the articles, see the Sources and References section of this guide.

Speech and Learning

Many people with NBEA-related syndrome had developmental delay and language delays or impairment.

  • 21 out of 33 people had developmental delay (64 percent)
  • 25 out of 35 people had language delays or impairment (71 percent)

Behavior

Nearly one-third of people who have the syndrome had behavior issues, including aggression and attention-deficit/hyperactivity disorder (ADHD). About one-half had autism or features of autism.

  • 7 out of 24 people had behavior issues (29 percent)
  • 4 out of 24 people had aggression (16 percent)
  • 4 out of 24 people had ADHD (17 percent)
  • 19 out of 35 people had autism or features of autism (54 percent)
29%
7 out of 24 people had behavior issues.
17%
4 out of 24 people had aggression.
17%
4 out of 24 people had ADHD.
54%
19 out of 35 people had autism or features of autism.

Brain

Nearly two-thirds of people who have the syndrome had seizures. Seizures were most likely to begin between 1 years and 4 years of age. People in this group often had abnormal electroencephalograms (EEGs).

  • 22 out of 35 people had seizures (63 percent)
  • 9 out of 22 people had achieved freedom from seizures (41 percent)
Human head showing brain outline

Mobility

Children who have the syndrome started walking from 11 months to 3.5 years of age. One-third had low muscle tone. Low muscle tone can delay motor skills, such as rolling over, sitting, crawling, and walking. One-quarter of people moved in an unusual way, such as walking with a wide, uncoordinated gait.

  • 8 out of 24 people had low muscle tone (33 percent)
  • 3 out of 24 people had uncontrolled muscle contractions, also called dystonia (13 percent)
  • 6 out of 24 people had unusual movements (25 percent)
33%
8 out of 24 people have low muscle tone.
13%
3 out of 24 people had uncontrolled muscle contractions, also called dystonia.
25%
6 out of 24 people have unusual movements.

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

  • Wang X. et al. Journal of Neuroscience, 20, 8551-8565, (2000). Neurobeachin: A protein kinase A-anchoring, beige/Chediak-higashi protein homolog implicated in neuronal membrane traffic – www.ncbi.nlm.nih.gov/pubmed/11102458
  • Castermans D. et al. Journal of Medical Genetics, 40, 352-356, (2003). The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism – www.ncbi.nlm.nih.gov/pmc/articles/PMC1735479
  • Mulhern MS. et al. Annals of Neurology, 84, 788-795, (2018). NBEA: Developmental disease gene with early generalized epilepsy phenotypes – www.ncbi.nlm.nih.gov/pubmed/30269351
  • Pan, Z., Chen, C., Yin, F., & Peng, J. (2022). Genotypic and phenotypic spectra of NBEA-related neurodevelopmental disorder with epilepsy: A case series and literature review. World Journal of Pediatrics, 18(9), 636-641. https://pubmed.ncbi.nlm.nih.gov/35852783/

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