Parental Profiles Modify Genetic Predisposition To Autism

David H. Ledbetter, Ph.D., FACMG Executive Vice President & Chief Scientific Officer, Geisinger Health System Danville, PA Interview with:
David H. Ledbetter, Ph.D., FACMG

Executive Vice President &
Chief Scientific Officer, Geisinger Health System
Danville, PA 17822

Medical Research: What is the background for this study? What are the main findings?

Dr. Ledbetter: One of the biggest challenges in clinical care and research of children with autism and related neurodevelopment disorders is the remarkable clinical variability between individuals. This heterogeneity is reduced, but still significant, when considering individuals who have neurodevelopment disorders due to the identical genetic mutation such as deletion 16p11.2. We proposed that family background, genetic or environmental, may contribute to the variability in cognitive, behavioral and motor performance profiles of children with a sporadic (new) mutation in 16p11.2. Our study confirmed that a significant portion of the clinical variability seen in these children is due to the performance level of their parents and unaffected siblings and suggested that this may be due in part to genetic background effects as these traits are all known to have very high heritability.

Medical Research: What should clinicians and patients take away from your report?

Dr. Ledbetter: There has been confusion in the literature around the observation that some children with a genetic disorder have intellectual disability, but not autism, while other children with the identical mutation have autism, but not intellectual disability. Our study demonstrates that the deletion 16p11.2 mutation has a deleterious effect on cognitive and social performance for all children, but the resulting performance level and clinical status (affected vs. normal) is influenced  by the performance level of the parents. These correlations are not yet strong enough to allow accurate clinical predictions for individual children early in life, but are an important step in the direction of understanding the contributions to individual variability and guiding our future research towards personalizing and optimizing treatment.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Ledbetter: We need much more research on the factors that contribute to individual variability in cognitive, social and motor performance in children with specific genetic disorders so that we can perform clinical research to optimize each child’s ultimate performance outcome. Important considerations for this research include treating these neurodevelopmental domains as dimensional traits rather than dichotomous, categorical buckets and the use of family studies to begin to understand the relative contribution of other genetic and environmental factors to ultimate performance levels.



Last Updated on December 13, 2014 by Marie Benz MD FAAD