SLC6A1-NDD: Clinical Overview
Every year, SLC6A1 CONNECT organises a symposium in the United States.
One of the speakers at the 2024 symposium was Dr. Marie Varnet, MD, from UT Southwestern and Children’s Health Dallas. We thank her for her valuable and insightful presentation.
Below are some of the highlights of her presentation.
Prevalence and Discovery
​
Mutations in the SLC6A1 gene are estimated to affect approximately 1 in 38,000 births. These disorders were first described between 2014 and 2015, primarily in children presenting with absence seizures and myoclonic-atonic seizures.
Development and Regression
​
Developmental delay is a hallmark feature in children with SLC6A1 mutations, observed in approximately 95% of cases. Many individuals also experience regression, meaning the loss of previously acquired skills in areas such as language and motor function.
This regression can follow different patterns: in some cases, it occurs as a single episode, with or without subsequent recovery; in others, it recurs over time. Regression is often associated with epileptic seizures, autism spectrum disorder, and severe language impairment.
Epilepsy
​
Epilepsy is a very common symptom in individuals with SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD). However, early diagnosis can be challenging, as the electroencephalogram (EEG) is often normal in the early stages of life.
The most commonly observed seizure types are: absence seizures, followed by atonic, myoclonic, and tonic-clonic seizures.
Note: We have intentionally chosen not to summarise the section of the video related to pharmacological treatment, as we do not provide medical advice.
Anyone interested in sharing experiences or seeking support is warmly invited to join our self-help groups.
Movement Disorders
​
In addition to cognitive and behavioural challenges, more than half of patients with SLC6A1-NDD also present with movement disorders. These may include: clumsiness, poor coordination, tremors, ataxia or abnormal gait.
Maladaptive behaviour
​
Problematic behaviours are among the most challenging aspects of caring for someone with SLC6A1-NDD. Approximately 78% of patients exhibit hard-to-manage behaviours such as frequent emotional outbursts, poor frustration tolerance, impulsivity and, in more than half of cases, aggression.
Traditional behavioural and educational strategies are often ineffective in managing these behaviours.
Sleep disorders
​
56% of patients with SLC6A1-NDD suffer from sleep disorders. The most common issues include difficulty falling asleep, frequent night awakenings, restless sleep and early awakening.
Autism Spectrum Disorder
​
Autism spectrum disorder (ASD) is common in children with SLC6A1-NDD, with a prevalence of 61%, equally distributed between males and females.
One of the early signs is often developmental regression, such as the loss of language or other skills. However, the presence of these symptoms does not necessarily mean a diagnosis of ASD will follow.
SAMPLE CASE
During her presentation, Dr. Marie Varnet presents a representative case study, divided into five parts. We believe it accurately reflects the experiences of many families. For this reason, we chose to transcribe it exactly as it was presented, without making any edits or summaries. In the narrative, the speaker addresses a hypothetical physician treating a girl with an SLC6A1 mutation.
PART 1
​
A 2-year-old girl presents to the neurology clinic for delayed development and abnormal spells.
​
She was born on time with no complications after a normal pregnancy. She had many issues with reflux as an infant and parents struggled to find a formula she could tolerate.
​
She never seemed as interested in toys or her environment as her older siblings.
She was mildly delayed in sitting up, crawling, and walking, but now at the age of 2 she can walk and run; however, she seems less coordinated than her peers. At times she will fall suddenly without clear cause.
Since infancy, parents have noticed odd episodes of blinking and staring. She has previously had an EEG around the age of 10 months that was normal.
​
Cooing and babbling were on time; she said her first word a little after 1 year old and gained a handful more words but over the last couple of months has stopped speaking altogether.
Tantrums occur just like any 2-year-old; however, parents feel that her outbursts are more intense and difficult to soothe compared to their older children.
PART 2
​
Because you are worried about the description of the events she is experiencing and the developmental regression, you begin an examination.
Routine EEG was abnormal.
WES (Whole Exome Sequencing) returned with a pathogenic variant in SLC6A1.
PART 3
​
You have been working on seizure control which has required adjustments, but is overall going well. Because you know how important early intervention is, you sent in referrals for speech therapy, physical therapy, occupational therapy, and autism evaluation.
​
Luckily, you live in an area with somehow little to no wait time for therapies and autism evaluation. By the time the family follows up with you, she is established in therapies and they have an autism diagnosis. Family is relieved to have names for what has been going on with their daughter, but remain anxious about the future.
PART 4
​
Your patient is now 7 years old. Seizures have been under control for years, but parents are more stressed and frustrated than ever due to their daughter’s difficult behaviour. She has frequent meltdowns that are difficult to predict. At times she can become aggressive, both during meltdown and sometimes seemingly out of nowhere. She is in full-time ABA but her therapists are also unsure how to proceed. At this point they are considering discharging her from their centre.
​
To make matters worse, your patient only sleeps about 4 hours a night. She struggles with bedtime, then wakes early, unable to fall back asleep. The parents are exhausted.
PART 5
​
Your patient is doing much better after a long journey of different medications, therapies, and behaviour modification.
You’ve done a wonderful job partnering with the family to address the needs of the child and caregiver.
​
We would like to once again thank Dr. Marie Varnet for her talk, “Clinical Presentation of SLC6A1-NDD”, and SLC6A1 CONNECT for allowing us to use this valuable video.