Abstracts

Rationale:
Pathogenic variants in KCNB1, the gene that encodes the voltage-gated potassium channel KV2.1, cause a developmental and epileptic encephalopathy (DEE) with a broad clinical spectrum. Previous reports have focused on the epilepsy phenotype and cognitive impairments. In addition to these features, many patients also have functional limitations and additional medical issues including dysautonomia. Here we sought to examine the relationship between functional abilities, dysautonomia, and epilepsy phenotype in KCNB1-DEE.
Method:
Patients with pathogenic or likely pathogenic variants in KCNB1 were recruited to participate in an online study constructed in CLIRINX. Questions focused on seizures, 18 autonomic symptoms (including cardiac, respiratory, temperature regulation, diaphoresis, drooling, and abnormal pupillary response), and functional level (walking independence, eating independence, communication skills, hand use, and for children ≥3 years, simple academic skills). Data were analyzed in SAS © and R with chi-square and other non-parametric tests as appropriate for the data. Cramer’s V was used as an omnibus measure of association for complex contingency tables.
Results:
Thirty-four parent-respondents reported for their participant-children who had a median age of 8.0 years (IQR 5.3-12.0 years, max 22.9 years) and of whom 17 (50%) were female. Twenty-five (74%) children had ongoing seizures (one or more within the past 6 months), 7 (21%) had remote seizures ( >=6 months ago), and for 2 (6%) it was unclear. One or more dysautonomic symptoms were reported in 26/34 (76%) participants, with a median of 2 symptoms (IQR 0-4, max 14). The most common autonomic symptoms reported were temperature dysregulation (18, 53%) and diaphoresis (12, 35%). With regard to functional abilities, 9/33 (27%) participants were wheel-chair dependent, 16/32 (50%) participants were dependent for eating, 13/31 (42%) participants were ineffective or inconsistent communicators, 8/33 (24%)  participants had no purposeful hand grasp, and 22/28 (78%) participants ≥3 years old had no academic/pre-academic skills. The number of dyautonomic features or number of categories of dysautonomic features was significantly correlated (p< 0.05) with worse functional levels for gross motor function, eating independence, communication skills, as well as academic skills. Temperature and breathing dysregulation categories were each significantly correlated with worse functional levels in 4 out 5 functional domains.
Conclusion:
Parents of children with KCNB1-Encephalopathy frequently describe dysautonomic features, seizures, and functional impairments. Dysautonomic features are highly correlated with level of functional impairment. Our findings emphasize the importance of asking about the presence dysautonomic features in addition to detailed seizure history, as this may reflect disease severity and level of functional impairment.
Funding:
:NIH 2KL2TR001424-05A1, Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and the Pediatric Epilepsy Research Consortium, Dallas.