Parental Performance Influences Genetic Neurodevelopmental Disability

Andres Moreno De Luca, MD Investigator and Resident Physician Autism & Developmental Medicine Institute Department of Radiology Geisinger Health System Danville, PA 17822 MedicalResearch.com Interview with:
Andres Moreno De Luca, MD
Investigator and Resident Physician
Autism & Developmental Medicine Institute
Department of Radiology Geisinger Health System
Danville, PA 17822

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

Response: The main finding of our study is that family background contributes to the variability in cognitive, behavioral, and motor performance seen in children with 16p11.2 deletions, and perhaps other genetic syndromes, and this may be attributed in part to genetic background effects.

In the general population the best predictor of a child’s outcomes in traits such as cognitive ability, height, BMI, etc. is the biparental mean performance in such domains and this is due in part to genetic background. For example, if a child’s parents have IQ scores of 130 and 110, it is expected that the child will have an IQ within 2 standard deviations of 120 (bi-parental mean). However, when studying individuals with genetic conditions, most researchers tend to overlook the influence of familial/genetic background on the affected child’s outcomes and commonly attribute the manifestations (or lack thereof) to the genetic mutation alone.

This creates confusion when studying children with neurodevelopmental disorders, such as autism, which show significant clinical variability, as some children with a specific genetic mutation (e.g. deletion 16p11.2) may have intellectual disability without autism, while other children with the same mutation may have autism without intellectual disability. Based on these observations, some researchers have argued that deletion 16p11.2 is incompletely penetrant. However, our study showed that the 16p11.2 deletion has a detrimental effect on cognitive and behavioral performance for all children, but the clinical status (affected vs. unaffected) and ultimate performance level is influenced by the parental performance.

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

Response: That we should take into account family background and the performance level of first-degree family relatives on multiple quantitative, heritable traits when studying individuals with neurodevelopmental disabilities. Assessing the level of functioning of unaffected family members can aid clinicians in the evaluation of children with neurodevelopmental disabilities by establishing a quantitative profile of strengths and weaknesses which can be used to determine a child’s expectations.

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

Response: We recommend to obtain data and include first-degree family relatives on future studies of genetically-caused neurodevelopmental disorders to allow for intrafamilial analyses, which can provide valuable information regarding the effect size of the genetic variant of interest and the intraclass correlation between parents (or siblings) and proband.

Citation:

Moreno-De-Luca A, Evans DW, Boomer KB, et al. The Role of Parental Cognitive, Behavioral, and Motor Profiles in Clinical Variability in Individuals With Chromosome 16p11.2 Deletions. JAMA Psychiatry. Published online December 10, 2014. doi:10.1001/jamapsychiatry.2014.2147.

 

MedicalResearch.com Interview with:, & Andres Moreno De Luca, MD (2015). Parental Performance Influences Genetic Neurodevelopmental Disability MedicalResearch.com