INS NYC 2024 Program

Poster	Poster Session 10 Program Schedule 02/17/2024 09:00 am - 10:15 am Room: Shubert Complex (Posters 1-60) Poster Session 10: Neurodevelopmental \| Congenital Conditions Final Abstract #47 Comparing Neurobehavioral Profiles of Genetic Disorders with Shared Mechanisms Sydney Jacobs, Boston Children's Hospital, Boston, United States Seyda Kilic, Tufts University, Medford, United States LeeAnne Snyder, Simons Foundation, New York, United States Katrina Boyer, Boston Children's Hospital, Boston, United States Siddharth Srivastava, Boston Children's Hospital, Boston, United States Category: Genetics/Genetic Disorders Keyword 1: genetic disorders Keyword 2: pediatric neuropsychology Objective: Advances in genetic testing have contributed to the burgeoning genetic landscape of neurodevelopmental disorders (NDD), a crucial step towards improving their diagnosis, prognosis, and treatment. One set of genes that has been consistently associated with several NDDs include those primarily involved in regulating transcription. Although described separately for each genetic disorder, the degree to which clinical symptomatology is shared across these conditions has not yet been established. Thus, the primary goal of this study was to compare neurobehavioral symptoms of SETBP1, HIVEP2, MED13L, and CSNK2A1 disorders, which we expected to be similar due to their commonality of transcriptional regulation. To further identify individuals at-risk for behavioral concerns, we also explored the effect of various developmental factors on symptom burden across the total sample. Participants and Methods: Data were collected through Simons Searchlight from individuals who had pathogenic or likely pathogenic variants in the genes SETBP1, HIVEP2, MED13L, and CSNK2A1 (N = 115). Participants ranged in age from 8 to 330 months (mean = 87.37, SD = 58.06) and were 48.7% female. Adaptive, social-emotional, and behavioral functioning were assessed via several caregiver questionnaires: Vineland Adaptive Behavior Scales, Second Edition (VABS-II); Social Responsiveness Scale (SRS); Social Communication Questionnaire, Lifetime (SCQ); and the Child Behavior Checklist (CBCL, Preschool and School-Age versions). Exploratory variables included birth weight, gestational age, number of prior neurological diagnoses, and autism diagnosis. Total and subscale scores for each questionnaire were compared across genetic variants using a Kruskal-Wallis H Test. Correlation analyses were also run to assess the relationship between exploratory variables and total scores of each questionnaire across the entire sample. Results: As anticipated, scores on behavioral questionnaires generally did not differ across genetic conditions. However, a significant difference emerged on the CBCL, Preschool Internalizing Problems scale (χ²=8.63, p=0.035), with post-hoc pairwise comparison identifying a significant difference in the mean rank scores between CSNK2A1 (60.0) and SETBP1 (49.91) specifically. Exploratory analyses did not indicate significant correlations between gestational age or birth weight with total scores. Number of neurological diagnoses significantly correlated with total scores on most questionnaires, including VABS-II (τ_b=-0.21, p=0.046), SRS (τ_b=0.35, p=0.002), SCQ (τ_b=0.44, p<0.001), and CBCL, Preschool (τ_b=0.28, p=0.030). Additionally, prior autism diagnosis was significantly associated with total VABS-II (τ_b=-0.31, p=0.007), SRS (τ_b=0.32, p=0.006), and SCQ (τ_b=0.24, p=0.022) scores. Conclusions: Overall, results reflect similar neurobehavioral profiles across the identified genetic conditions, suggesting that a shared mechanism of action may contribute to similar clinical features. Differences in the CBCL subscale indicated that preschool-aged participants with the CSNK2A1 variant specifically may exhibit more emotional symptoms, such anxiety, withdrawal, and emotional reactivity. Across all conditions, a greater number of neurological co-morbidities was correlated with more social and behavioral symptoms, as well as lower adaptive functioning. Additionally, autism was associated with low adaptive functioning and, unsurprisingly, more social difficulties, although did not correlate with general behavioral or emotional symptoms.

Poster

02/17/2024
09:00 am - 10:15 am
Room: Shubert Complex (Posters 1-60)

Poster Session 10: Neurodevelopmental | Congenital Conditions

Final Abstract #47

Comparing Neurobehavioral Profiles of Genetic Disorders with Shared Mechanisms

Sydney Jacobs, Boston Children's Hospital, Boston, United States
Seyda Kilic, Tufts University, Medford, United States
LeeAnne Snyder, Simons Foundation, New York, United States
Katrina Boyer, Boston Children's Hospital, Boston, United States
Siddharth Srivastava, Boston Children's Hospital, Boston, United States

Category: Genetics/Genetic Disorders

Keyword 1: genetic disorders
Keyword 2: pediatric neuropsychology

Objective:

Advances in genetic testing have contributed to the burgeoning genetic landscape of neurodevelopmental disorders (NDD), a crucial step towards improving their diagnosis, prognosis, and treatment. One set of genes that has been consistently associated with several NDDs include those primarily involved in regulating transcription. Although described separately for each genetic disorder, the degree to which clinical symptomatology is shared across these conditions has not yet been established. Thus, the primary goal of this study was to compare neurobehavioral symptoms of SETBP1, HIVEP2, MED13L, and CSNK2A1 disorders, which we expected to be similar due to their commonality of transcriptional regulation. To further identify individuals at-risk for behavioral concerns, we also explored the effect of various developmental factors on symptom burden across the total sample.

Participants and Methods:

Data were collected through Simons Searchlight from individuals who had pathogenic or likely pathogenic variants in the genes SETBP1, HIVEP2, MED13L, and CSNK2A1 (N = 115). Participants ranged in age from 8 to 330 months (mean = 87.37, SD = 58.06) and were 48.7% female. Adaptive, social-emotional, and behavioral functioning were assessed via several caregiver questionnaires: Vineland Adaptive Behavior Scales, Second Edition (VABS-II); Social Responsiveness Scale (SRS); Social Communication Questionnaire, Lifetime (SCQ); and the Child Behavior Checklist (CBCL, Preschool and School-Age versions). Exploratory variables included birth weight, gestational age, number of prior neurological diagnoses, and autism diagnosis. Total and subscale scores for each questionnaire were compared across genetic variants using a Kruskal-Wallis H Test. Correlation analyses were also run to assess the relationship between exploratory variables and total scores of each questionnaire across the entire sample.

Results:

As anticipated, scores on behavioral questionnaires generally did not differ across genetic conditions. However, a significant difference emerged on the CBCL, Preschool Internalizing Problems scale (χ²=8.63, p=0.035), with post-hoc pairwise comparison identifying a significant difference in the mean rank scores between CSNK2A1 (60.0) and SETBP1 (49.91) specifically. Exploratory analyses did not indicate significant correlations between gestational age or birth weight with total scores. Number of neurological diagnoses significantly correlated with total scores on most questionnaires, including VABS-II (τ_b=-0.21, p=0.046), SRS (τ_b=0.35, p=0.002), SCQ (τ_b=0.44, p<0.001), and CBCL, Preschool (τ_b=0.28, p=0.030). Additionally, prior autism diagnosis was significantly associated with total VABS-II (τ_b=-0.31, p=0.007), SRS (τ_b=0.32, p=0.006), and SCQ (τ_b=0.24, p=0.022) scores.

Conclusions:

Overall, results reflect similar neurobehavioral profiles across the identified genetic conditions, suggesting that a shared mechanism of action may contribute to similar clinical features. Differences in the CBCL subscale indicated that preschool-aged participants with the CSNK2A1 variant specifically may exhibit more emotional symptoms, such anxiety, withdrawal, and emotional reactivity. Across all conditions, a greater number of neurological co-morbidities was correlated with more social and behavioral symptoms, as well as lower adaptive functioning. Additionally, autism was associated with low adaptive functioning and, unsurprisingly, more social difficulties, although did not correlate with general behavioral or emotional symptoms.