Age-related white matter differences in children with neurofibromatosis type 1 compared to controls

Neurofibromatosis type 1 (NF1) is a common genetic condition in which 30-70% of children experience learning challenges including deficits in attention, executive function, and working memory. White matter pathways have been implicated in these cognitive functions; yet, they have not been well characterized in NF1. In this retrospective cohort study, we used diffusion MRI tractography to examine the microstructural properties of major white matter pathways in 20 children with NF1 aged 1 year to 18 years relative to 20 age-and sex-matched controls. An automated approach was used to identify and extract mean diffusivity (MD) and fractional anisotropy (FA) of eight cerebral white matter pathways bilaterally and the anterior and posterior part of the corpus callosum. Compared to controls, children with NF1 had significantly increased MD and significantly decreased FA in multiple white matter pathways including the anterior thalamic radiation, cingulate, uncinate fasciculus, inferior fronto-occipital fasciculus, arcuate fasciculus, and corticospinal tract. Differences in MD and FA remained significant after controlling for intracranial volume. In addition, MD and FA differences between children with NF1 and controls were greater at younger than older ages. These findings have implications for understanding the etiology of the neurocognitive deficits seen in many children with NF1. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was made possible through a generous donation from the Greathouse Family Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Stanford University School of Medicine gave ethical approval for this work (protocol# 28674). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.