Authors :
Presenting Author: Anne Berg, PhD – Northwestern University Feinberg School of Medicine and DEE-P Connections
Jason Lerner, MD – Biohaven Pharmaceuticals, Inc; John Millichap, MD, FAAN, FAES – Neurology – Northwestern University Feinberg School of Medicine and Precision Epilepsy; Gil L'Italien, PhD – Biohaven Pharmaceuticals, Inc; Vlad Coric, MD – Biohaven Pharmaceuticals, Inc; Michele Potashman, PhD – Biohaven Pharmaceuticals, Inc
Rationale:
KCNQ2-DEE is a rare, heterogenous condition that manifests as developmental delays combined with neurological comorbid signs and symptoms. While seminal work has described KCNQ2-DEE patients at the group-level, relatively little information is available about the severity and variability of the condition within individuals. A collation of a large number of individual patient-level disease experience data, beyond case reports and a limited case series, has yet to be published.
Methods:
Data obtained from a cross-sectional survey (2018 through 2020) of parents of children aged two years and above with KCNQ2-DEE was analyzed across four functional ability domains (mobility, communication, hand use, and eating abilities). Separately, we also considered cortical visual impairment (CVI) as another marker of disease severity. Each of these aspects were considered core to the condition and clinically meaningful to families. The functional domains were assessed with classifications systems commonly employed in the pediatric rehabilitation field. The associations of severe functional impairment across these domains and the number of domains with severe impairment were examined to determine which, if any, impairments tended to occur in isolation or in combination with other impairments. Data were analyzed with methods appropriate for nonparametric dichotomous and ordinal data.
Results:
Data for the four domains were available for N=51 affected children. Communication impairment and eating dependencies were apparent across the vast majority of the cohort, with only N=3/51 (6%) and N=2/51 (5%), respectively, having some degree of independent function in these domains. Severe communication impairment was the most prevalent comorbidity (N=34/51, 67%) and was present regardless of the number of other domains impacted. Severe impairment in the other domains were present in 26 (51%) for mobility, 7 (14%) for hand use, and 22 (43%) for eating. The number of affected domains was 0 (N=13 children), 1 (N=13), 2 (N=6), 3 (N=12) and 4 (N=7). Several patients had multiple domains severely impact (Figure 1). Of the 13 participants with only one severely affected domain, that domain was most often communication (11/13), and 2 had isolated mobility impairments. Hand use was the least likely to be impaired; however, when it was, all three other domains were also severely impaired. The presence of CVI increased with the number of affected domains from 8% for zero domains to 71% for four domains (p< 0.0001 for trend).