Identifying the Role of Parental Traits in Explaining Phenotypic Variability in Children with Neurogenetic Developmental Disorders: towards early individualized intervention

2020 Award: $39,718

Children with genetic syndromes affecting brain development are at substantially increased risk for neuropsychiatric disorders, but symptom variability has hindered the development of effective treatments. In this project, we will determine whether family genetic background can explain symptom variability in children with neurogenetic disorders. Identifying cost-effective predictors of specific areas of risk is critical in guiding the development of personalized early interventions.

Need/Problem: Children diagnosed with Fragile X syndrome and Down syndrome are at substantially increased risk for developing neuropsychiatric disorders including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Despite a known genetic cause for each syndrome, substantial clinical variability exists among children with both syndromes, suggesting an important role for genetic background in shaping child outcomes.

Grant Summary: We will collect behavioral data from biological parents to model the relative role of genetic background in explaining behavioral, neurobiological, and clinical variability in young children with Fragile X and Down syndrome who have been followed since infancy.

Goals and Projected Outcomes: Our primary goal for this study is to identify the role of genetic background in informing cognitive, clinical, and brain phenotypes in individuals with Fragile X and Down syndrome. The information gained from this study will inform future work designed to predict outcomes and alert clinicians to specific areas of neurodevelopmental vulnerability for young children diagnosed with a genetic syndrome affecting brain development.

Jessica Girault, PhD

Grant Details: Participants will include 25 children with Fragile X syndrome and 25 children with Down syndrome and their families, recruited through two longitudinal NIH-funded studies. Child participants receive extensive behavioral and clinical testing and undergo magnetic resonance imaging at each study visit. As part of this Foundation of Hope Award, parents will complete a behavioral battery involving cognitive and behavioral testing. Parental traits will be modeled as predictors of offspring behavior, clinical symptomology, and brain structure. Families affected by Fragile X syndrome will also provide DNA samples to determine the role of Fragile X mutation architecture in explaining brain and behavioral development and risk for neuropsychiatric disorders.