Is cognitive profiling in NF1 still optional? A systematic review of current assessment practices
Andrea Santangelo1,2, Alessandra Sardi2, Luca Bergonzini3,4,5
1Pediatric Neurology and Muscular Diseases Department, IRCCS G. Gaslini Institute, Genoa, Italy.
Background/Objectives:
Neurofibromatosis type 1 (NF1) is a common genetic disorder often accompanied by cognitive, behavioral, and neurodevelopmental disorders. While tumor-related manifestations are well-documented, less attention has been paid to standardized assessment of neuropsychological profiles in affected children. This systematic review aimed to evaluate current assessment practices for cognitive, behavioral, and neurodevelopmental domains in pediatric NF1.
Methods:
A systematic search was conducted across PubMed, Scopus, Web of Science and Embase databases (April 2015-April 2025) using predefined keywords and Boolean logic. Eligibility criteria included original studies assessing neurodevelopmental, cognitive, motor, behavioral, or social-emotional outcomes in pediatric NF1 populations (0-18 years). Exclusion criteria comprised adult-only samples, reviews, non-English publications, and animal models. Study selection followed PRISMA guidelines.
Results:
From 414 identified records, 84 studies met inclusion criteria. A total of 35 domains were explored, with cognitive functioning (n = 41), executive functioning (n = 33), behavior (n = 28), and attention (n = 22) most frequently assessed. Over 110 assessment tools were used, including the Wechsler Intelligence Scales, BRIEF, CBCL, and Conners Rating Scales. However, 52.4% of studies focused on children aged 6 years or older, indicating that preschool-aged children remain underrepresented in the literature and limiting opportunities for early identification. Few studies employed validated diagnostic instruments for ASD or ADHD (e.g., ADOS-2, ADI-R, and K-SADS), while most relied on symptom rating scales such as the CBCL or Conners questionnaires, which assess behavioral traits but do not establish a clinical diagnosis.
Conclusion:
Current assessment practices in pediatric NF1 are heterogeneous and often neglect early developmental windows. The integration of standardized, age-appropriate tools and early neurodevelopmental screening-supported by interdisciplinary teams including neuropsychomotor therapists-may improve detection and management of NF1-related neurocognitive phenotypes. A shared framework for assessment is essential to enhance clinical care and research comparability.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/view/CRD420251119558, identifier CRD420251119558.
