Abstracts

Cognition and Behavior in Children and Young Adults with SCN2A-Developmental and Epileptic Encephalopathy (DEE): An Initial Evaluation of the Developmental Profile, Fourth Edition (DP-4)

Abstract number : 3.456
Submission category : 11. Behavior/Neuropsychology/Language / 11B. Pediatrics
Year : 2022
Submission ID : 2232986
Source : www.aesnet.org
Presentation date : 12/5/2022 12:00:00 PM
Published date : Nov 22, 2022, 05:29 AM

Authors :
Natasha Ludwig, PhD – Kennedy Krieger Institute/Johns Hopkins School of Medicine; Mary Wojnaroski, PhD – Nationwide Children’s Hospital/Ohio State University; Ariela Kaiser, MA – University of Illinois at Chicago; Katherine Paltell, MA – University of Illinois at Chicago; Lindsey Evans, MA – Illinois Institute of Technology; Jenny Downs, PhD – Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia; Chere T. Chapman, MBA – Ardea Outcomes; Gabrielle Conecker, MPH – DEE-P Connections (Wishes for Elliott); JayEtta Hecker, MS – DEE-P Connections (Wishes for Elliott); Keith Coffman, MD – Children’s Mercy; Leah Schust Myers, BA – FamilieSCN2A Foundation; Terry Jo Bichell, PhD – Combined Brain; Anne Berg, PhD – Northwestern Feinberg School of Medicine

This is a Late Breaking abstract

Rationale: SCN2A-associated developmental and epileptic encephalopathy (DEE) is associated with severe impairment in cognition, communication, motor function, social function, and adaptive skills. Commonly used clinical outcome measures for these domains have substantial floor effects and are thus not fit for purpose for clinical trials. Recent FDA guidances emphasize the need for appropriate measures, especially in trials for rare diseases. This study seeks to explore the initial suitability of the Developmental Profile, Fourth Edition (DP-4) Parent/Caregiver Checklist, a new, easy to administer caregiver questionnaire, in capturing a range of neurodevelopmental outcomes in children with SCN2A-DEE.

Methods: Ten children and young adults with pathogenic mutations in SCN2A attending the FamilieSCN2A Foundation conference (July 2022) participated (Mage=8.2 years, SD=5.62, range 3.4-20.4; Nmale=8; N=7 had epilepsy). Parents completed the five electronically administered DP-4 scales: Cognitive, Communication, Physical, Social-Emotional, and Adaptive Behavior. Child cognition was also measured directly with the Bayley-4 Cognitive scale (administered out of age range) and parents also completed a standardized caregiver interview-based measure of adaptive functioning, the Vineland-3. Standard Scores (SSs) and age-equivalents (AEs) on the DP-4 and AEs on the Bayley-4 Cognitive scale and Vineland-3 subdomains were examined.

Results: Eighty to ninety percent of individuals earned the lowest possible SSs across DP-4 scales; however, AEs offered greater range and variability of scores with AEs ranging from a < 1 to 38-month-level depending on domain (Table 1). Relative weaknesses were observed in the areas of Communication and Social-Emotional functioning compared to Cognition and Adaptive Behavior, consistent with the high prevalence of autism in this population (all p< .05; Table 1). DP-4 AEs were strongly correlated with their respective Bayley-4/Vineland AEs (Table 2). The frequency of lowest possible AE scores was comparable between the DP-4 and Bayley-4/Vineland-3, with the exception of the DP-4 Social-Emotional scale where 70% of children obtained the lowest possible AE (i.e., floor effect) compared to only 0-10% on the Vineland-3 social subdomains (Table 1).

Conclusions: The DP-4 is a new parent questionnaire-based measure of child neurodevelopmental outcomes that requires relatively fewer resources than direct in-person assessments like the Bayley-4 and extensive parent interviews like the Vineland-3. Given high correlations with the Bayley-4 and Vineland-3, DP-4 AEs may provide a quick and accessible way to capture non-seizure outcomes in children and young adults with SCN2A-DEE. Future work via The Inchstone Project will explore the validity and utility of the DP-4 in larger samples and in other DEEs characterized by severe impairment to inform use in clinical and research contexts.

Funding: The Inchstone Project (Wishes for Elliott) and FamilieSCN2A Foundation
Behavior