Abstracts

Rationale: Mutations in the SLC6A1 gene have been associated with clinical findings of developmental delay and epilepsy (often epilepsy with myoclonic atonic seizures). However, there has been limited exploration of the early phase of disease expression and comorbid aspects of the phenotype. This report describes the clinical features seen in three patients with SLC6A1 mutations. Methods: Three patients with SLC6A1 mutations were identified in our clinical practice. Their medical charts were reviewed, and data were gathered on their age, sex, initial clinical presentation, specific genetic mutation, development, epilepsy, and stereotypes. Results: Of the three patients identified, two were initially evaluated due to developmental delays and regression or plateauing of skills. Their genetic mutations were identified by the GeneDx Autism/Intellectual Disability panel. These two have had repeated evaluations for abnormal movements, but have had normal EEGs and no clear seizures up to the age of 2 years. The third patient was initially evaluated for brief spells of slumping to the ground and was ultimately diagnosed with epilepsy with atypical absence seizures. Her genetic mutation was identified by the Invitae Epilepsy panel. All three patients have developmental delays. The first has profound delays with skills in all domains less than the 1st percentile for age. When treated with four weeks of high dose steroids he had an improvement in development, but remains profoundly delayed. The second has moderate delays in cognitive and motor skills. The third has mild delays in language and gross motor skills which have improved during treatment of her epilepsy with levetiracetam. All three patients have been noted to have abnormal movements consisting of repeated spells of eye blinking with forceful eye closure lasting a few seconds at a time. This is sometimes associated with head tilting. Two have repetitive tapping of hand to chin. Two twirl their hands and feet. Most of these movements have been captured on EEG and are not seizures. Clinically they are most consistent with stereotypes and their appearance is quite similar between patients. In the two patients who have received treatment, their stereotypes decreased in frequency as their development improved (and as seizures improved in the patient with epilepsy). In the patient with epilepsy, her stereotypes preceded the onset of her seizures by over a year. Conclusions: SLC6A1 mutations are relatively newly described and have a broad clinical phenotype. In a group of three patients seen in our practice, specific stereotypies such as hand to chin tapping and blinking with forceful eye closure were common findings which have not previously been described in the literature. Funding: No funding