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β-Propeller protein–associated neurodegeneration (BPAN) is a rare, X-linked condition caused by pathogenic variants in the WDR45 gene that result in a defect of autophagy. Classified as a disorder of neurodegeneration with brain iron accumulation, β-propeller protein–associated neurodegeneration is associated with severe neurologic impairments. With the anticipation of future therapeutic trials, this project characterizes the family's perspective of the impact of disease and defines Health Concepts (HC). Children with a molecularly confirmed diagnosis of β-propeller protein–associated neurodegeneration were enrolled in a prospective natural history study. We administered the Vineland Adaptive Behavior Scales–Third Edition and provided health-related quality of life questionnaires to 42 caregivers. Questionnaires included Pediatric Quality of Life Inventory–Generic Core and Pediatric Quality of Life Inventory–Family Impact modules, Caregiver Priorities and Child Health Index of Life with Disabilities, and Caregiver TBI-CareQoL. The Vineland Adaptive Behavior Scales–Third Edition (n = 42) captured the family's perspective that communication was more affected compared with socialization, activities of daily living (ADL), and motor skills (P <.0001, P <.0001, P =.0053, respectively). Similarly, on the Caregiver Priorities and Child Health Index of Life with Disabilities (n = 26), Pediatric Quality of Life Inventory–Generic Core (n = 27), CareQol (n = 26), and Pediatric Quality of Life Inventory–Family Impact (n = 27), communication abilities, as well as social functioning and activities of daily living, were noted to be most impacted. Through the use of standardized surveys and outcome assessments, we establish the effects of β-propeller protein–associated neurodegeneration on caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. The identified HC will inform the future identification of concept of interest and selection of appropriate clinical outcome assessments through the administration of patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Over 300 million people globally are affected by rare diseases, many of which present predominantly with neurologic symptoms. Rare neurologic disorders pose significant diagnostic and therapeutic challenges including delayed diagnoses, limited treatment options, and a shortage of specialists. However, advancements in diagnostics, particularly next-generation sequencing and expansion of newborn screening, have significantly shortened the time to diagnosis for many of these disorders. Concurrently, the past decade has witnessed exponential development of new treatments for rare neurologic diseases, with several approved gene therapies and more trials under way. A range of targeted therapies now offers hope for not only symptomatic management but also for disease modification. As treatments transition from clinical trials to clinical practice, the responsibility of identifying and monitoring patients may increasingly fall on the general neurologists. This evolving therapeutic landscape highlights the urgent need to enhance our understanding of this new class of medications and the details on clinical eligibility and monitoring of patients with diseases that have approved gene therapies. This article provides a comprehensive overview of gene-targeted therapies currently available for neurologic disorders, with a focus on their mechanisms, challenges, and post-treatment considerations., Competing Interests: G. Porcari and J.W. Collyer have nothing to disclose. L.A. Adang is a consultant to Orchard Therapeutics, Biogen, and Takeda. D.S. Rajan is site PI for clinical trials from Denali, Takeda, Prevail, Ultragenyx, Regenxbio therapeutics, is a consultant for Sanofi, Takeda and has grant funding from the National Scleroderma Foundation. Go to Neurology.org/NG for full disclosures., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)