Cognitive and behavioral problems in children with neurofibromatosis type 1: challenges and future directions

Cognitive and behavioral disorders affect nearly 80% of all children with the neurofibromatosis type 1 inherited cancer syndrome, and are among the most significant clinical manifestations for patients and their families. One of the barriers to successful therapeutic intervention is the wide spectrum of clinical phenotypic expression, ranging from visuospatial learning problems to social perceptual deficits (autism). Leveraging numerous small-animal models of neurofibromatosis type 1, several promising targets have been identified to treat the learning, attention, and autism spectrum phenotypes in this at-risk population. In this review, we provide an up-to-date summary of our current understanding of these disorders in NF1, and propose future research directions aimed at designing more effective therapeutic approaches and clinical trials.