SCN1B-Related Syndrome
SCN1B-related syndrome is also called atrial fibrillation, familial, 13 (ATFB13), developmental and epileptic encephalopathy-52 (DEE52), and generalized epilepsy with febrile seizures plus type 1 (GEFSP1). For this webpage, we will be using the name SCN1B-related syndrome to encompass the wide range of variants observed in the people identified.
What is SCN1B-related syndrome?
SCN1B-related syndrome happens when there are changes in the SCN1B gene. These changes can keep the gene from working as it should.
Key Role
The SCN1B gene plays an important role in brain function.
Symptoms
Because the SCN1B gene is important for brain activity, many people who have SCN1B-related syndrome have:
- Developmental delay
- Brugada syndrome, which is a condition that causes abnormal heartbeats
- Generalized epilepsy with febrile seizures
What causes SCN1B-related syndrome?
SCN1B-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 SCN1B 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 SCN1B plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that SCN1B-related syndrome is often the result of a de novo variant in SCN1B. Many parents who have had their genes tested do not have the SCN1B genetic variant found in their child who has the syndrome. In some cases, SCN1B-related syndrome happens because the genetic variant was passed down from a parent.
Some people have variants to their genes that prevent them from working properly. A variant in one copy of the SCN1B gene has little or no effect on their health — because one working copy is enough. People who have one working copy of the gene and one non-working copy of the gene are called ‘carriers’. Some people have genes where both copies do not work as they should. In these cases, the person has inherited non-working copies of the gene from both parents. This can lead to physical issues, developmental issues, or both.
Autosomal dominant conditions
SCN1B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in SCN1B they will likely have symptoms of SCN1B-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
Autosomal recessive conditions
SCN1B-related syndrome can also be an autosomal recessive genetic condition. To be affected with symptoms of an autosomal recessive genetic condition, a person has two damaging variants on both copies of their SCN1B. For someone with an autosomal recessive genetic syndrome, every time they have a child they will pass on one non-working copy of SCN1B.
Autosomal Recessive Genetic Syndrome
Why does my child have a change in the SCN1B-related syndrome gene?
No parent causes their child’s SCN1B-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 foreseen or stopped.
What are the chances that other family members of future children will have SCN1B-related syndrome?
Autosomal dominant conditions
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 SCN1B-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 SCN1B-related syndrome, the sibling’s risk of having a child who has SCN1B-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing SCN1B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SCN1B-related syndrome.
- If one biological parent has the same genetic variant causing SCN1B-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 SCN1B-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
Autosomal recessive conditions
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 the same biological parents to a child with an autosomal recessive genetic condition, having another child who has SCN1B-related syndrome is almost always 25 percent.
- The chance of two carrier parents having a child who is also a carrier is 50 percent. Carriers are not expected to have symptoms.
- The chance of them having a child who is not a carrier at all is 25 percent.
For a person who has SCN1B-related syndrome, the risk of having a child who has the same syndrome depends on their partner.
- If their partner is a carrier, they have a 50 percent chance of having a child who has the syndrome and a 50 percent chance of having a child who is a carrier.
If their partner is not a carrier, they have nearly a 0 percent chance of having a child who has the syndrome and a 100 percent chance of having a child who is a carrier.
How many people have SCN1B-related syndrome?
As of 2024, at least 100 people with SCN1B-related syndrome have been described in medical research.
Do people who have SCN1B-related syndrome look different?
People who have SCN1B-related syndrome may not look different.
How is SCN1B-related syndrome treated?
Scientists and doctors have only just begun to study SCN1B-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 SCN1B-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.
Behavior and development concerns linked to RORB-related syndrome
SCN1B-related syndrome can be caused by one genetic variant in SCN1B (referred to as the autosomal dominant condition) or two genetic variants in SCN1B (referred to as the autosomal recessive condition).
People with one genetic variant in SCN1B (autosomal dominant condition)
People with one genetic variant in SCN1B do not always have medical features. These variants might have been inherited throughout the family.
Learning
Very rarely, people with one genetic variant in SCN1B had developmental delay or intellectual disability. Less than 5 people have been reported to date.
Brain
Some people had seizures. People in the same family might have different seizure types.
Sometimes people had febrile seizures, which are seizures that occur in childhood during fevers. Other common seizure types were focal seizures and generalized tonic–clonic seizures.
People with one genetic variant in SCN1B might be more at risk of sudden unexpected death in epilepsy (SUDEP).
Heart
Some people with one genetic variant in SCN1B developed cardiac arrhythmic disorders, which are conditions of irregular heartbeat.
People with two genetic variants in SCN1B (autosomal recessive condition)
People with two genetic variants in SCN1B usually have medical features associated with both SCN1B-related syndrome and early infantile developmental and epileptic encephalopathy (DEE).
Learning and behavior
Most but not all people had developmental delay before or after seizure onset. Some people had developmental regression after seizure onset and/or autism.
Brain
Almost all people with two genetic variants in SCN1B had seizures. This type of condition is called epileptic encephalopathy (EE), which is a group of severe epilepsy syndromes that can cause more cognitive and behavioral impairments. These seizures might be resistant to medications.
Other symptoms included walking defects, low muscle tone (hypotonia), and sleep disorders.
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 SCN1B: www.simonssearchlight.org/research/what-we-study/scn1b
- Simons Searchlight SCN1B Facebook community: https://www.facebook.com/groups/scn1b
Sources and References
The content in this guide comes from published studies about SCN1B-related syndrome.
- Fang, H., Hu, W., Kang, Q., Kuang, X., Wang, L., Zhang, X., Liao, H., Yang, L., Yang, H., … & Wu, L. (2023). Clinical characteristics and genetic analysis of pediatric patients with sodium channel gene mutation-related childhood epilepsy: A review of 94 patients. Frontiers in Neurology, 14, 1310419. https://pubmed.ncbi.nlm.nih.gov/38174099/
- Zhu, Z., Bolt, E., Newmaster, K., Osei-Bonsu, W., Cohen, S., Cuddapah, V. A., Gupta, S., Paudel, S., Samanta, D., … & Naik, S. (2022). SCN1B genetic variants: A review of the spectrum of clinical phenotypes and a report of early myoclonic encephalopathy. Children (Basel), 9(10). 1507. https://pubmed.ncbi.nlm.nih.gov/36291443/