Abstracts

Rationale: Dravet Syndrome is an intractable childhood epilepsy syndrome with onset in the first year of life and most often associated with an SCN1A mutation. Associated comorbidities in children with Dravet Syndrome include a slowing or stagnation of cognitive development, behavioral disturbances, and gait abnormalities. In our clinical practice, several patients with Dravet Syndrome were noted to have endocrine dysfunction. This has not been reported in the literature to date.Methods: A retrospective chart review was performed at a single institution. Eligibility criteria were a clinical diagnosis of Dravet Syndrome and genetic confirmation of the diagnosis. Sixty eligible children were identified. Data was entered into a REDCap database. Records were reviewed for demographic information, serologic evidence of endocrine abnormality, (including growth hormone, sex hormones, cortisol, and thyroid testing), concurrent anti-epileptic medication, and positive family history of endocrine disease.Results: 60 children were included in the cohort, 53% male, age range 11 months to 20 years, taking an average of 2.7 anticonvulsant medications per patient. Twenty-six children underwent serologic endocrine testing. 6/14 (43%) children tested for growth hormone deficiency had low levels of IGF-1, a prevalence of 10% within the entire cohort. Two children with low IGF-1 levels had further testing that confirmed growth hormone deficiency. One of these children was found to have pan-hypopituitarism with additional thyroid and cortisol abnormalities. Thyroid function tests (TSH, free T4, and total T4) were the most commonly assessed endocrine lab and were abnormal in 6/23 (26%) of children tested. Sex hormone levels, including follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, were also checked in 13 patients. Lab results that were checked infrequently included parathyroid hormone, T3, estradiol, androstendione, prolactin, and insulin. The three most commonly prescribed anticonvulsant medications included clobazam, valproate, and stiripentol in 70%, 48%, and 32% of children, respectively. There was a documented positive family history of endocrine disease in 17% (n=10) of children in the entire cohort. 4/6 (66%) children with a positive family history of endocrine disease also had abnormal endocrine laboratory testing.Conclusions: Comorbidities in children with Dravet Syndrome may involve more systems than previously reported and may include endocrine dysfunction. At least, one-third of children tested for endocrine abnormalities had serologic evidence of dysfunction, most notably evidence of low growth hormone. Further research is needed in this area.