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

Abstract

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.

Keywords::

• attention
• autism
• cognitive and behavioral
• learning and memory
• monogenic
• mouse models
• neurofibromatosis type 1
• NF1
• preclinical
• single gene

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Cognitive and behavioral disorders affect the vast majority of children with neurofibromatosis type 1 and account for much of the lifetime morbidity and societal impact associated with the condition.

• Most current treatment strategies are based on approaches developed for the general population.

• Small-animal models and in vitro studies have revealed molecular pathways (RAS, cAMP and dopamine) affected by impaired neurofibromin function.

• Clinical trials are currently underway to evaluate some of these discovered targeted therapies.

• Successful development of targeted therapeutics will require further studies using tractable experimental models and clinical trials designed to test specific hypotheses in pre-selected patient cohorts.

Notes