Objective:

To report behavior concerns in SLC6A1 Neurodevelopmental Disorder (SLC6A1-NDD), a major concern for families.

Background:

SLC6A1-NDD is rising in recognition as a cause of epilepsy and autism. SLC6A1 haploinsufficiency disrupts GABA homeostasis resulting in neurobehavioral changes presenting with developmental delay and later with seizures. Behavior often becomes the most disruptive symptom with age, and clinician time is frequently spent managing behaviors more than seizures.

Design/Methods:

 Patient records reviewed of confirmed genetic SLC6A1-NDD diagnosis collected from specialty clinics and natural history study participants from UTSW and CHOP.

Results:

A total of 58 patient records (29 M: 29 F) were reviewed. Of these, 45 were reported to have behavior concerns. While some are mild, a significant proportion (53%) have aggression concerns, with a trend of low frustration tolerance and impulsivity contributing to outbursts. The most frequently reported concerns related to tantrums/meltdowns that might include aggression, self-injury, and impulsivity. Out of 30 individuals, 16 utilized medications meant to modify behavior, most frequently antipsychotics and ADHD medications. 

Conclusions:

As medicine moves toward precision therapies, the symptoms that most affect everyday functioning of patients and their caregivers should be considered. Often, it is not the seizures causing daily strife in SLC6A1-NDD, but instead, concerns with behavior arising from differences in development that contribute to impulsivity, low frustration tolerance, and anxiety. There is an emerging pattern of worsening behavior after seizure control that is difficult to manage. A medication currently under clinical trial for SLC6A1-NDD has had success controlling seizures and anecdotally improved behavior.  It is behavior and development, more than seizures, that prevents participation in society. It is not just the child that suffers, but also the caregivers who sacrifice their roles in society in numerous ways. Managing behavior is paramount in the clinic and home thus, behavior and development concerns must be part of determining precision therapy success.