SYNGAP1-Related Syndrome

SYNGAP1–related syndrome happens when there are changes in the SYNGAP1 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 SYNGAP1-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 SYNGAP1-related syndrome, the sibling’s risk of having a child who has SYNGAP1-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing SYNGAP1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SYNGAP1-related syndrome. 
• If one biological parent has the same genetic variant causing SYNGAP1-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 SYNGAP1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 388 people with SYNGAP1-related syndrome have been identified in a medical clinic. The first case of SYNGAP1-related syndrome was described in 2015.

People who have SYNGAP1-related syndrome may look slightly different. Appearance can vary and can include some but not all of these features:

• Almond-shaped opening of the eyes
• Slight open-mouthed appearance
• Broad nasal bridge
• Long nose
• Full lower lip

Scientists and doctors have only just begun to study SYNGAP1-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 SYNGAP1-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.

Speech and learning

Most children who have SYNGAP1-related syndrome showed some degree of intellectual disability, ranging from mild to severe. They required special educational support. Almost all children who have SYNGAP1-related syndrome had speech delay. The average age of speaking the first word was 24 months. But, some people were non-verbal.

• 147 out of 147 people had developmental delay and intellectual disability (100 percent)

Behavior

Some people who have SYNGAP1-related syndrome had autism or features of autism, challenging behaviors, anxiety, and sleep problems. Some of the behavioral issues were aggressive behaviors, self-injurious behavior, and irritability.

• 100 out of 147 people had features of autism (68 percent)
• 100 out of 147 people had behavioral issues (68 percent)
• 35 out of 147 people had an anxiety disorder (24 percent)
• 90 out of 147 people had sleeping issues (61 percent)

Brain

Aside from ID, the second most common feature people with SYNGAP1-related syndrome had was epilepsy. Common seizure types included generalized seizures, absence or atypical absence seizures, atonic seizures, reflex seizures, and tonic-clonic seizures.

• 123 out of 147 people had epilepsy (84 percent)

Mobility

Most had low muscle tone, also called hypotonia. Low muscle tone can cause delays in developmental milestones, such as sitting and walking, as well as a wide-based or unsteady walk. Average age of walking was 20 months.

• 69 out of 147 people had ataxia or abnormal gait (47 percent)

Feeding and digestion

About one-half of people with SYNGAP1-related syndrome had feeding issues. Some people needed a feeding tube. Feeding difficulties included swallowing issues, oral aversion, and failure to thrive.

• 69 out of 147 people had feeding difficulties (47 percent)

Eyes

Some people with SYNGAP1-related syndrome had crossed eyes.

• 32 out of 147 people had crossed eyes (22 percent)

Adults

A small number of people with SYNGAP1-related syndrome over the age of 18 years old have been described in medical research. The oldest person was 65 years old. Most people were dependent on caregivers for activities of daily living, and about one-half could walk independently.