SNAP25-Related Syndrome

SNAP25-related syndrome happens when there are changes in the SNAP25 gene. These changes can keep the gene from working as it should.

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 SNAP25-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 SNAP25-related syndrome, the sibling’s risk of having a child who has SNAP25-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing SNAP25-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SNAP25-related syndrome. 
• If one biological parent has the same genetic variant causing SNAP25-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 SNAP25-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, about 32 people with SNAP25-related syndrome have been identified in a medical clinic.

People with SNAP25-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:

• Vertical fold of skin that covers the inner corner of the eye
• Crowding of teeth
• Skin folds at the eyes, also called epicanthal folds

Scientists and doctors have only just begun to study SNAP25-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 SNAP25-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.

Learning and Speech

All people with SNAP25-related syndrome had developmental delay or intellectual disability, and speech delay or impairment. About 1 in 3 people had a developmental regression associated with seizures in which they lost words that they previously attained.

• 25 out of 25 people had developmental delay (100 percent)
• 21 out of 21 people had intellectual disability (100 percent)
• 18 out of 19 people had speech delay or impairment (95 percent)
• 5 out of 19 people had a developmental regression (26 percent)

The severity of intellectual disability varied among people:

• 5 out of 20 people had mild intellectual disability (25 percent)
• 6 out of 20 people had moderate intellectual disability (30 percent)
• 5 out of 20 people had severe intellectual disability (25 percent)
• 4 out of 20 people had profound intellectual disability (20 percent)

Behavior

Some people with SNAP25-related syndrome had behavioral issues, such as features of autism and repetitive behaviors (stereotypic behavior).

• 3 out of 18 people had autism (17 percent)
• 4 out of 18 people had stereotypic behavior (22 percent)

Brain

Many people with SNAP25-related syndrome had seizures, including epileptic spasms, generalized seizures, focal seizures, and tonic-clonic seizures. The age of seizure onset occurred around 12 months, with a range of onset between birth to 12 years old. About 1 in 10 people developed refractory seizures. One-half of people were treated with more than 3 antiepileptic medications. Response to seizure medications was inconsistent.

• 19 out of 25 people had seizures (76 percent)

Seizure types varied among people:

• 7 out of 17 people had generalized or focal, bilateral tonic-clonic seizures (41 percent)
• 6 out of 17 people had absence-like seizures (35 percent)
• 5 out of 17 people had epileptic spasm seizures (29 percent)
• 4 out of 17 people had myoclonic, tonic, and atonic seizures (24 percent)

People with SNAP25-related syndrome had brain changes seen on magnetic resonance imaging (MRI), lower than average muscle tone (hypotonia), cortical visual impairment, and movement disorders, such as ataxia, dystonia, and tremor.

• 6 out of 22 people had brain changes seen on MRI (27 percent)
• 13 out of 21 people had hypotonia (63 percent)
• 6 out of 19 people had cortical visual impairment (32 percent)
• 8 out of 22 people had ataxia (36 percent)
• 4 out of 21 people had dystonia (19 percent)
• 2 out of 21 people had tremor (10 percent)

Growth

Some people with SNAP25-related syndrome had bilateral clubfeet, joint hypermobility, and hip dysplasia.

• 5 out of 21 people had bilateral clubfeet (24 percent)
• 4 out of 21 people had joint hypermobility (19 percent)
• 2 out of 21 people had hip dysplasia (10 percent)

SNAP25 Foundation

The SNAP25 Foundation is dedicated to raising awareness of the genetic disorder caused by mutations in the gene Snap25, and working towards finding a cure.

• https://snap25.org/

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 SNAP25 – www.simonssearchlight.org/research/what-we-study/snap25