Neurodevelopmental and Psychiatric Studies in Children and Adolescents With Neurofibromatosis Type I: A Comprehensive Scoping Review

A comprehensive synthesis of the broad range of neurodevelopmental and psychiatric manifestations in NF1 is needed to identify knowledge gaps and future directions for NF1 research. In the following scoping review, we identify and summarize the scope of research that examines neurodevelopmental and psychiatric manifestations, both as categorical diagnoses and symptoms, in children and adolescents with neurofibromatosis type 1 (NF1). As a secondary objective, we summarize studies examining the association between intellectual impairment and psychopathology in children and adolescents with NF1. A literature search was conducted in three databases (Medline, PsychINFO, EMBASE) from inception to the third week of November 2024 with no restrictions on year of publication or publication type. Search terms related to neurofibromatosis, psychiatric symptoms and disorders, intellectual disability, and learning disorders. A total of 112 studies were identified that met the review inclusion criteria. The majority of studies focused on children aged 6-12 years (n = 106; 95%) and adolescents (n = 87; 78%) with fewer studies in the preschool age (n = 43; 38%) and the least number of studies in the infant age group (n = 10; 9%). The majority of these involved clinical cohorts (n = 94; 84%). The intellectual domain was assessed in 77 studies (69%), the academic domain in 29 studies (26%), and the psychiatric domain in 88 studies (79%). Thirteen studies (12%) assessed all three domains (intellectual, academic, and psychiatric). Many studies assessed for ADHD diagnosis (n = 24; 21%) or symptomatology (n = 43; 38%) or for autism diagnosis (n = 12; 11%) or symptomatology (n = 26; 23%). Few studies assessed for anxiety diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%) or for depression diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%). Twelve studies (11%) examined the association between intellectual impairment and psychopathology. There is a need for studies that use standardized assessments to reliably distinguish between traits and diagnoses and to capture whether children meet criteria for more than one disorder (co-morbidity). There is also a need for studies examining the association between intellectual impairment and psychopathology in children with NF1. A better understanding of the neurodevelopmental and psychiatric manifestations that children with NF1 are at greatest risk for can help shape clinical care guidelines, improve parental psychoeducation, and optimize the use of effective interventions.