SLC6A1-Related Syndrome

SLC6A1-related syndrome happens when there are changes to the SLC6A1 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 SLC6A1-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 SLC6A1-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 SLC6A1-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 SLC6A1-related syndrome is 50 percent.

For a person who has SLC6A1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 209 people with SLC6A1-related syndrome have been identified in a medical clinic.

People who have SLC6A1-related syndrome do not look different.

Scientists and doctors have only just begun to study SLC6A1-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 SLC6A1-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/…t-is-epilepsy/seizure-types

Some people inherit an SLC6A1 variant from a parent who may or may not have medical features. About 20 out of 118 people with SLC6A1-related syndrome inherited the variant from a parent. Siblings and first-degree relatives carrying the variant usually have variable symptoms that are milder than the symptoms of the person with SLC6A1-related syndrome.

Speech and Learning

Many people with SLC6A1-related syndrome had developmental delay or intellectual disability. Most people had moderate to mild intellectual disability. Eleven people with average IQ were described in the research literature, and some people had learning disorders and/or epilepsy. Developmental delay was often reported by parents before seizure onset. Some people had developmental regression around the age of 3 years old.

• 98 out of 119 people had developmental delay or intellectual disability (82 percent)
• 15 out of 119 people had developmental regression (13 percent)

Behavior

Behavioral disorders occurred in about 1 out of 3 people with SLC6A1-related syndrome. About one-half of people had autism or features of autism, and a few had attention-deficit/hyperactivity disorder (ADHD).

• 41 out of 119 people had behavioral disorders (35 percent)
• 64 out of 119 people had autism or features of autism (54 percent)
• 20 out of 119 people had ADHD (17 percent)

Brain

Most people with SLC6A1-related syndrome had seizures. Seizure types included absences with or without eyelid myoclonia, atonic, myoclonic, tonic–clonic (grand mal), and focal seizures. People often had more than one seizure type. In a study of adults with SLC6A1-related syndrome, 7 out of 11 adults had seizures that were refractory.

• 169 out of 204 people had seizures (83 percent)
• 94 out of 116 people had absences with or without eyelid myoclonia seizures (81 percent)
• 70 out of 116 people had atonic seizures (60 percent)
• 58 out of 116 people had myoclonic seizures (50 percent)
• 22 out of 116 people had tonic–clonic seizures (19 percent)
• 9 out of 116 people had focal seizures (8 percent)

Other findings

Some people with SLC6A1-related syndrome had sleep difficulties, lower than average muscle tone, and movement disorders. The most common movement disorders were tremors and ataxia.

• 16 out of 24 people had sleep issues (67 percent)
• 56 out of 83 people had lower than average muscle tone (68 percent)
• 31 out of 83 people had movement disorders (37 percent)