STXBP1-Related Syndrome
STXBP1 is also known as STXBP1 encephalopathy or STXBP1-E.
What is STXBP1-related syndrome?
STXBP1-related syndrome happens when there are changes to the STXBP1 gene. These changes can keep the gene from working as it should.
Key Role
The STXBP1 gene plays a key role in how brain cells communicate.
Symptoms
Because the STXBP1 gene is important in brain cell function, many people who have STXBP1-related syndrome have:
- Seizures
- Movement challenges
- Autism spectrum disorder
What causes STXBP1-related syndrome?
Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the STXBP1 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 STXBP1 plays a key role in development, de novo changes in this gene can have a meaningful effect.
Research shows that STXBP1-related syndrome is often the result of a de novo change in STXBP1. Many parents who have had their genes tested do not have the STXBP1 gene change found in their child who has the syndrome. In some cases, STXBP1-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 STXBP1 gene
No parent causes their child’s STXBP1-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 or future children will have STXBP1-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 STXBP1-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 STXBP1-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 STXBP1-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 STXBP1-related syndrome is 50 percent.
For a person who has STXBP1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have STXBP1-related syndrome?
As of 2019, about 200 people in the world with changes in the STXBP1 gene had been described in medical research. The first case of STXBP1-related syndrome was described in 2008. Scientists expect to find more people who have the syndrome as access to genetic testing improves.
Do people who have STXBP1-related syndrome look different?
People who have STXBP1-related syndrome generally don’t look different.
How is STXBP1-related syndrome treated?
Scientists and doctors have only just begun to study STXBP1-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 STXBP1-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
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 STXBP1-related syndrome
Learning
Almost everyone who has STXBP1-related syndrome has some level of intellectual disability.
- About 90 percent of people have severe intellectual disability.
Behavior
- About 20 percent of people who have the syndrome have repetitive behaviors.
- About 17 percent of people have autism.
Medical and physical concerns linked to STXBP1-related syndrome
Brain
- Almost everyone — 95 percent — who has the syndrome has seizures at some point in their lives. More than one-half have early-onset seizures.
Sitting and walking
More than one-half of people who have the syndrome are unable to walk on their own.
- 24 out of 45 people are unable to walk on their own.
Muscle tone
Most people who have STXBP1-related syndrome have low muscle tone.
Other motor concerns
Issues with motor coordination and motor control are common.
Where can I find support and resources?
STXBP1 Foundation
STXBP1 Foundation is dedicated to finding a cure for STXBP1-Related Disorders (STXBP1-RD) while improving the lives of our patients and families. Founded in 2017, STXBP1 Foundation is a parent-led advocacy organization. STXBP1-RD is a rare neurodevelopmental disorder caused by changes in the STXBP1 gene. With an incidence of approximately 1 in 30,000 live births, STXBP1-RD is one of the most common genetic causes of epilepsy.
- STXBP1 Foundation Website – stxbp1disorders.org
- STXBP1 Foundation – Facebook page
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 STXBP1 – www.simonssearchlight.org/research/what-we-study/stxbp1
- Simons Searchlight STXBP1 Facebook community – Simons Searchlight STXBP1 Facebook community
Other resources:
- Unique – STXBP1 Guidebook
- Geisinger Developmental Brain Disorder Gene Database – STXBP1
Sources and references
The content in this guide comes from published studies about STXBP1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Khaikin Y. et al. GeneReviews, (2016). STXBP1 encephalopathy with epilepsy www.ncbi.nlm.nih.gov/books/NBK396561
- Stamberger H. et al. Neurology, 86, 954-962, (2016). STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy www.ncbi.nlm.nih.gov/pubmed/26865513