Abstracts

Rationale: The Rare-Epilepsy Network (REN) is an initiative created by caregivers of children with rare epilepsies to encourage research. Ten rare epilepsy organizations together with Epilepsy Foundation, RTI and Columbia University became the REN and a survey was opened on September 28, 2014. Since then, 600 caregivers have registered or entered data covering demographics, diagnosis of epilepsy, seizure features, medications, surgery, genetics, EEG, MRI, comorbidities, and birth data. We undertook analyses aimed at assessing comorbidity commonalities and differences across syndromes as there is almost no information on this topic.Methods: Data were collected by Web-based survey. We assessed 16 comorbidity classes and multiple disorders within each class (Table 1) in 9 syndromes with sufficient comorbidity data. Analyses computed pairs of comorbidity classes within each syndrome when comorbidity pairs accounted for > 50% of all subjects in a syndrome. Single comorbidities that were not part of comorbidity pairs were also assessed. Additionally, we examined the proportion with each comorbidity class across syndromes and determined the mean burden of endorsed disorders in the comorbidity class.Results: Caregivers entered data on 363 affected individuals. Age of diagnosis was between 0 and 5 years for Aicardi, CDKL5, and Dravet syndrome with the majority under 1 year. In syndromes affecting girls (Aicardi, CDKL5, PCHD19) only PCDH19 had diagnoses over age 5. The diagnosis age range for other syndromes covered a larger age span. Affected individuals were predominantly non-Hispanic, White with a high annual family income. Syndromes with single comorbidities, not part of pairs, were observed for sleep in PCDH19 and Dravet (Table 2). Other single comorbidities were vision for Dup15q, endocrine for hypothalamic hamartoma (HH) and oral/dental for LGS. The number of comorbidity pairs were few in these syndromes. Comorbidity pairs (Table 2) showed commonalities across Aicardi, CDKL5, PMS, and TS, although dermatological findings in TS, and oral/dental issues in CDKL5 distinguished these disorders. Among syndromes affecting only girls, PCDH19 had only one comorbidity pair, compared to 13 for Aicardi and 23 for CDKL5, the most affected syndrome. In 3 syndromes with mutations in the mTOR pathway, the number of comorbidity pairs were 23 for CDKL5, 16 for PMS, and 11 for TS. Comorbidity clusters present at more than 50% for each syndrome were observed only in pairs for Dravet, HH, LGS, and PCDH19. We found 3 quartets in Aicardi and 1 in TS, a quintet in PMS, and 2 sextets in CDKL5. The frequency of comorbidities was high across most syndromes and the burden of disorders within comorbidity classes varied by syndrome.Conclusions: There are overlapping factors across the rare epilepsies, but sufficient information in the most burdened syndromes to determine characteristics that separate syndromes. Across syndromes affecting one pathway at different stages, slightly different comorbidity pairs manifest and the burden of comorbidity is not uniform across syndromes.