Neurodevelopmental Profiles for RASopathies

Rene Pierpont, Ph.D.
International meeting on genetic syndromes of the Ras/MAPK pathway

The last few decades have seen rapid progress toward establishing neuropsychological profiles associated with Ras/MAPK pathway syndromes. Among affected individuals, cognitive functioning can vary from significant global intellectual disability to mild delays in specific domains. In a subset of individuals, no significant learning or behavior problems are seen. Research using animal models has begun to reveal neurobiological sources of differences in learning and memory processes in the RASopathies, as well as suggest potential methods to circumvent these differences. However, additional research is needed to identify the most useful neurocognitive targets of intervention in humans.

Development of effective educational or pharmacological mechanisms that will impact long-term outcomes depends on progress in a number of areas. In particular, it will be critical to identify key individual characteristics that can predict response to intervention in any given domain. While current research has established that variation in intellectual functioning and adaptive skills can be partially explained by the differences in genotype, wide variability in outcomes can be observed even among people with the same mutations. Additional important characteristics associated with treatment response may include chronological age at intervention, presence of medical risk factors, and baseline level of functioning. Further, neuropsychological measurement instruments for clinical trials must be validated within the target population and evaluated for reliability and practice effects. As research in this area progresses, there is great promise to positively impact the lives of individuals with genetic syndromes of the Ras/MAPK pathway.