We are pleased to announce that Stanford Psychiatry’s Tamar Green, Associate Professor of Psychiatry and Behavioral Sciences, has received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, titled “Brain Developmental Trajectories of Noonan Syndrome: An Accelerated Longitudinal Study.”

Gain-of-function mutations in the #RAS/MAPK pathway, essential for brain development and function, cause #Noonan syndrome and related RASopathies that result in neurodevelopmental challenges in up to 90% of cases. Yet, the trajectory of brain development in Noonan syndrome remains unknown. The long-term goal of this project is to identify mechanisms underlying persistent cognitive and behavioral impairments in Noonan Syndrome and to guide developmentally timed interventions.

The objective of this project is to determine how striatal, cortical, white matter, and functional brain networks develop during adolescence, a critical period for RAS-dependent synaptic remodeling, circuit maturation, and emergence of sex differences, and how these trajectories relate to pubertal timing and behavioral outcomes. Noonan syndrome provides a genetically defined model to study neurodevelopment, enabling in vivo mechanistic mapping of brain network and structure in a clinically anchored cohort using cutting-edge multi-parametric neuroimaging.

The central hypothesis of this project is that brain development in Noonan syndrome diverges progressively from typically developing youth due to elevated RAS/MAPK signaling and altered pubertal timing. This will be the first longitudinal characterization of brain development through puberty in Noonan syndrome, disentangling RAS/MAPK-driven effects from hormonal influences. The expected outcomes include mechanistic insights into the neural basis of cognitive and behavioral impairments, and a foundation for developmentally timed interventions and precision neuroscience approaches in Noonan syndrome and related RASopathies.

“This study addresses a critical gap in understanding puberty in neurodevelopmental disorders, with potential implications for broader populations, with potential implications for #autism and other #neurodevelopmental conditions,” says Dr. Green. “Insights from this research will guide developmentally timed interventions to reduce disability and improve cognitive, behavioral, and overall functional outcomes in children with Noonan syndrome and related neurodevelopmental disorders.”

Dr. Green leads the Brain Imaging, Development, Genetics (BRIDGE) Lab, which integrates genetics, brain imaging, and clinical research to trace the biological pathways underlying neurodevelopmental conditions, beginning with genetic syndromes, and to translate those discoveries into precision treatments. Recent publications related to this work include "Genotype-phenotype correlations with autism spectrum disorder-related traits in Noonan syndrome and Noonan syndrome with multiple lentigines: a cross-sectional study," published in the journal Molecular Autism.

More Details

Read more details about the study at NIH RePORTER.