Authors :
Presenting Author: Morgan Jolliffe, Psy.D. – Children's Hospital Colorado
Carlyn Glatts, MD – Children's Hospital of Philadelphia
Michael Kaufman, MS – Children's Hospital of Philadelphia
Lori Silveira, PhD – University of Colorado, Anschutz Medical School
Megan Abbott, MD – Children's Hospital Colorado
Kaitlin Angione, MS – Children's Hospital Colorado
Hsiao-Tuan Chao, MD, PhD – Baylor College of Medicine
Jennifer Cross, MD – Weill Cornell
Kristin Cunningham, MS, OTR/L – Children's Hospital of Philadelphia
JoeyLynn Coyne, RT – Children's Hospital of Philadelphia
Kristen Fisher, DO – Baylor College of Medicine
Lauren Fishbein, PhD – Children's Hospital of Philadelphia
Zachary Grinspan, MD, MS – Cornell Weill Medicine
Kaitlyn Kennedy, BS – Children's Hospital Colorado
Maya Mosner, PhD – Children's Hospital of Philadelphia
Samuel Pierce, PT, PhD – Children's Hospital of Philadelphia
Jennifer Phillips, PhD – Stanford University
Ann Reynolds, MD – Children's Hospital Colorado
Sarah Ruggiero, MS, CGC – Children's Hospital of Philadelphia
Rayann Solidum, MS – Stanford University
Megan Stringfellow, BS – Children's Hospital Colorado
Sarah Tefft, MSN, RN, CRNP – Children's Hospital of Philadelphia
James Goss, PhD – STXBP1 Foundation
Charlene Son Rigby, BA, MBA – STXBP1 Foundation
Scott Demarest, MD – Children's Hospital Colorado
Ingo Helbig, MD – Children's Hospital of Philadelphia
Andrea Miele, PhD – Children's Hospital Colorado
Rationale:
STXBP1-RD are rare, monogenic, developmental epileptic encephalopathies characterized by developmental delay and intellectual disability. Behavioral features suggestive of autism are commonly reported; however, formal diagnosis is complicated by overlapping symptoms and a lack of validated assessment tools. The purpose of this study was to characterize autism-related behaviors in STXBP1-RD using the CARS-2, and to examine the relationships with cognitive functioning and age. While some association with cognitive functioning is expected, excessive influence would suggest shared measurement of cognition and autism severity, whereas minimal influence could reflect low CARS-2 sensitivity in the context of profound cognitive delays.
Methods:
CARS-2 data were collected from 43 individuals with STXBP1-RD, ranging in age from 1.5 to 19 years (M=6.2, SD=4.3). Cognitive abilities were assessed using the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4), with raw scores used to minimize floor effects. Several multiple linear regression models were used to assess the relationship between Bayley-4 cognitive raw scores and CARS-2 total scores (CARS-2-TS) across age-defined subgroups, controlling for age.
Results:
The mean CARS-2-TS score was 36.8 (SD=6.7), falling in the “severe” range (> 36.5) for autism symptoms. We found differing amounts of model fit and unique contribution in four multiple regression models spanning various age groups (see Table 1). Neither age nor Bayley Cognitive scores were associated with CARS-2-TS at the youngest ages (1.5 to 3-years). However, both age and Bayley Cognitive scores were significantly associated with CARS-2-TS with good model fit (F(2,29)=5.11, p=0.012) at age > 3-years. In all subsequent models, age was no longer associated with CARS-2-TS. In contrast, Bayley Cognitive scores were significantly associated with CARS-2-TS in all models of age > 3-years, > 4-years, and > 5-years with modest unique variance explained (Adjusted R2 ranging from 0.17 to 0.21). Model fit was significant at p= < 0.05 for > 3-years and > 4-years. Results indicated that for every 10-point increase in Bayley-4 raw scores, CARS-2-TS decreased by approximately 1.1 points.
Conclusions:
The relationship between cognitive functioning and autism symptom severity is complex in STXBP1-RD. Autism symptoms were highly prevalent, despite most children scoring around a 12-month cognitive age equivalent, highlighting the need for careful autism assessment in this population. Substantial variability in cognitive functioning at younger ages precludes a consistent relationship in autism symptom severity, though small sample size may be a confounder. Beyond 3-years, we observe a modest and consistent effect of cognition on autism symptoms, in line with literature in the general population. IQ is known to interact with autism severity in nonlinear ways, highly influenced by language skills. Future work should investigate the impact of language on autism severity.
Funding: The work was supported by the STXBP1 Foundation and the Center for Epilepsy and Neurodevelopmental Disorders (ENDD)