Developmental Patterns and Predictors of Academic Functioning in Children with Neurofibromatosis Type 1: Results from the Largest International Dataset Created by Integrative Data Analysis

Abstract

Background: Learning difficulties are frequently reported in children with neurofibromatosis type 1 (NF1), yet little is known about the extent and predictors of academic difficulties. We aimed to provide robust estimates of how academic functioning (math, reading, writing) varies across ages and how these trajectories differ across demographic and NF1-related disease factors.

Methods: This cross-sectional study used integrative data analysis to combine datasets collected between the years 1995-2022 from eight institutions in the United States, United Kingdom, and Australia, including population-based, clinically referred, and convenience samples of children with NF1. Academic functioning was assessed with Woodcock-Johnson Tests of Achievement or Wechsler Individual Achievement Test. Data were analyzed primarily using time-varying effect modeling.

Findings: Among the 1,521 participants, 46·5% were females; mean age was 11·2 years (SD = 3·62, range = 3-18 years). Participants’ academic functioning was significantly lower than the normative means across ages and decreased from early childhood to mid-adolescence. Academic trajectories varied across academic domains and demographic and NF1-related disease factors. Specifically, males had lower math scores at mid-childhood, lower reading and writing scores at mid-childhood to mid-adolescence. Non-White children had lower math and reading scores at mid-childhood and adolescence. Children with low parental education had lower math, reading, and writing scores at mid-childhood to mid-adolescence. Children with familial NF1 had lower math scores at mid-childhood and mid-to-late-adolescence, lower reading and writing scores at mid-childhood to mid-adolescence.

Interpretation: These results confirm a high risk of academic difficulties in children with NF1 and quantitatively illustrate the widening academic gap between children with and without NF1 from early childhood to mid-adolescence, while also exposing the variability within children with NF1 across demographic and NF1-related disease factors. These findings provide critical information for patient management and intervention development.

Funding: This research was supported by (a) federal funding from Congressionally Directed Medical Research Programs, Department of Defense, through Neurofibromatosis Research Program under Award number W81XWH2110504 and National Institutes of Health, National Cancer Institute, Center for Cancer Research, Intramural Research Program, (b) Florida State University Faculty Startup Funding, and c) the University of Kentucky Faculty Startup Funding.

Declaration of Interest: The authors declare no conflict of interest.

Ethical Approval: Data collection at each site was approved by the respective institutional review boards. The integrative data analysis was approved by the institutional review board of the University of Kentucky and Florida State University.

Keywords: neurofibromatosis type 1, genetic disorder, plexiform neurofibromas, academic functioning, math, reading, writing, developmental pattern, demographic, integrative data analysis, time-varying effect modeling