Symptoms & Manifestations
Every year, SLC6A1 Connect brings together families, researchers and clinicians at its annual symposium in the United States.
At the 2024 symposium, Dr. Marie Varnet, MD, presented an overview of the clinical manifestations of SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD), including how symptoms may appear and evolve over time. The type, combination and severity of symptoms can vary considerably from person to person.
This page highlights key information from her presentation, including a clinical example that illustrates some of the experiences families may encounter throughout their journey with SLC6A1-NDD.
Prevalence estimates for individual manifestations may vary between studies, depending on the population studied and the data available.
Dr. Marie Varnet, MD,
Children’s Hospital Colorado
University of Colorado
“Clinical Presentation of SLC6A1-NDD” — Dr. Marie Varnet, SLC6A1 Connect Symposium, 2024.
Video courtesy of SLC6A1 Connect.
Development and Regression
Developmental delay is one of the most common manifestations of SLC6A1-NDD.
Development may be delayed in different areas, including speech and language, learning and motor skills.
Some individuals may also experience developmental regression, meaning the loss of skills they had previously acquired.
Regression can follow different patterns. For some individuals, it may occur as a single episode, with or without subsequent recovery, while for others it may happen more than once over time.
Epilepsy
Epilepsy is one of the most common manifestations of SLC6A1-NDD.
Different types of seizures may occur. According to the clinical overview presented by Dr. Marie Varnet, the most commonly reported seizure types are absence seizures, followed by atonic, myoclonic and generalized tonic-clonic seizures.
Seizures may begin at different ages and can vary in frequency and severity.
Movement and Motor Difficulties
Movement and motor difficulties are common in people with SLC6A1-NDD and can affect mobility, coordination and everyday activities.
These may include tremor, difficulties with coordination and balance, and an unsteady gait.
Behavioural Challenges
Behavioural challenges are common in people with SLC6A1-NDD and can have a significant impact on everyday life for both individuals and their families.
These may include difficulties with attention, hyperactivity, impulsivity, anxiety, aggression and repetitive or self-injurious behaviours.
Sleep Disorders
Sleep difficulties are common in SLC6A1-NDD.
These may include difficulty falling asleep, frequent night-time awakenings, restless sleep and early waking.
Autism Spectrum Disorder
Autism spectrum disorder is commonly reported in individuals with SLC6A1-NDD.
Developmental regression, such as the loss of language or other previously acquired skills, may be an early sign. However, developmental regression does not necessarily mean that a child will later be diagnosed with autism spectrum disorder.
Understanding the Journey: A Clinical Example
In her presentation, Dr. Marie Varnet guides the audience through a clinical example of a healthcare professional following a patient with SLC6A1-NDD over time.
It brings together many of the manifestations described above and shows how developmental, neurological, behavioural and sleep-related challenges may emerge at different stages of childhood.
While every person with SLC6A1-NDD is different, this example may help families better understand some of the experiences that can be part of the journey.
PART 1: AGE 2 — FIRST SIGNS
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.
PART 2: DIAGNOSIS
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: EARLY INTERVENTION
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 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 she has received an autism diagnosis. The family is relieved to have names for what has been going on with their daughter, but remain anxious about the future.
PART 4: AGE 7 - NEW CHALLENGES
Your patient is now 7 years old. Seizures have been under control for years, but her 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 a 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: MOVING FORWARD
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 caregivers.
This example illustrates one possible journey with SLC6A1-NDD. Every individual is different, and symptoms, their severity and their evolution over time can vary considerably.
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.