Neuro-Ocular Vasculopathy Associated with Fanconi Anemia: A Clinical-Radiologic Phenotypic Case Series
- 1Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
Abstract
ObjectiveTo characterize the clinical, radiological, and pathological features of Neuro-Ocular Vasculopathy Associated with Fanconi Anemia (NOVA-FA).
MethodsSix patients with FA and neurological symptoms were phenotyped using retrospective chart review of clinical notes, neuroimaging, fluorescein angiogram, CSF analysis, and advanced research techniques including extensive infectious testing. Biopsies were reviewed in two patients.
ResultsNOVA-FA is defined by neurological symptoms, retinal vasculopathy, accumulation of punctate cerebellar lesions and/or large mass-like lesions with surrounding vasogenic edema. Histopathology showed vasculopathy without inflammation. Treatments with immunosuppressants appeared largely ineffective. Imaging and pathology suggest a non-inflammatory small vessel vasculopathy as the primary pathology.
InterpretationNOVA-FA is a recently identified condition that affects a subset of patients with FA and results in significant disability, including death. The etiology remains unknown, although the condition mimics features of the syndrome "retinal vasculopathy and cerebral leukodystrophy" which is due to dysfunction in DNA repair mechanisms. There is currently no known effective treatment.
Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSFanconi anemia is an inherited DNA-repair disorder, and only scattered case reports and small series have described an acquired neurological and ocular condition in a subset of these patients, and often presumed to be inflammatory. A consistent clinical-radiological definition, an understanding of the underlying mechanism, and evidence to guide treatment have been lacking.
What this study addsThis series of six patients provides the most detailed clinical, radiological and pathological characterization of the syndrome to date, proposes the name Neuro-Ocular Vasculopathy Associated with Fanconi Anemia (NOVA-FA) with provisional diagnostic criteria, and shows that histopathology, CSF and serum biomarkers, infectious testing and treatment response together point to a non-inflammatory small vessel vasculopathy rather than a primary immune-mediated or infectious process, closely mirroring the DNA-repair disorder RVCL.
How this study might affect research, practice or policyThe findings argue against reflexive immunosuppression, support earlier recognition of NOVA-FA through defined criteria, and reframe it as a DNA-repair-driven vasculopathy, motivating natural-history and mechanistic studies and the evaluation of vascular-targeted therapies as FA life expectancy rises and this phenotype becomes more common.
Social Media Summary If PublishedNone of the co-authors have a X handle that we would like to be tagged. There are scant case reports about this emerging neurologic syndrome in patients with Fanconi Anemia. This study contains the most robust neurological phenotyping of these patients and explores in-depth evaluations for molecular presence of inflammation.
Draft: A novel progressive neuro-ocular vasculopathy in Fanconi Anemia (NOVA-FA) presents with enhancing brain lesions and retinal changes. Likely due to microvascular DNA repair failure, not inflammation. #FanconiAnemia #Neurovascular #RareDisease
Related
- Sclerosing epithelioid fibrosarcoma of the bone: a systematic review of radiologic findings and associated clinical features
- Clinical, Radiologic, and Highest-Grade Assessment of Immune Checkpoint Inhibitor Pneumonitis in Non–Small Cell Lung Cancer
- Upper Extremity Fractures in Older Medicolegal Patients: Radiologic Characteristics and Factors Associated with Permanent Functional Impairment
- Diffuse stimulant-associated vasculopathy presenting with acute limb ischemia, compartment syndrome, and multifocal visceral infarction.
- Lenticulostriate vasculopathy in neonates: An imaging marker with heterogeneous clinical significance
BibTeX
@misc{waldrop2026neuroocular,
title = {{Neuro-Ocular Vasculopathy Associated with Fanconi Anemia: A Clinical-Radiologic Phenotypic Case Series}},
author = {G. Waldrop and D. Pandya and B. R. Smith and A. Soldatos and A. Abdelhak and N. Rasool and Y. Mina and C. Friend and R. Goldbach-Mansky and K. Y. Zhang and C.-H. G. Lucas and K. C. Zorn and S. Sidhu and A. J. Green and I. Tilton and S. J. Pleasure and N. Giri and C. Toro and A. Nath and M. R. Wilson and P. S. Ramachandran},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.26362096},
url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26362096v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Neuro-Ocular Vasculopathy Associated with Fanconi Anemia: A Clinical-Radiologic Phenotypic Case Series
AU - G. Waldrop
AU - D. Pandya
AU - B. R. Smith
AU - A. Soldatos
AU - A. Abdelhak
AU - N. Rasool
AU - Y. Mina
AU - C. Friend
AU - R. Goldbach-Mansky
AU - K. Y. Zhang
AU - C.-H. G. Lucas
AU - K. C. Zorn
AU - S. Sidhu
AU - A. J. Green
AU - I. Tilton
AU - S. J. Pleasure
AU - N. Giri
AU - C. Toro
AU - A. Nath
AU - M. R. Wilson
AU - P. S. Ramachandran
PY - 2026
DA - 2026/09/02
PB - medRxiv
DO - 10.64898/2026.09.02.26362096
UR - https://www.medrxiv.org/content/10.64898/2026.09.02.26362096v1
AB - ObjectiveTo characterize the clinical, radiological, and pathological features of Neuro-Ocular Vasculopathy Associated with Fanconi Anemia (NOVA-FA). MethodsSix patients with FA and neurological symptoms were phenotyped using retrospective chart review of clinical notes, neuroimaging, fluorescein angiogram, CSF analysis, and advanced research techniques including extensive infectious testing. Biopsies were reviewed in two patients. ResultsNOVA-FA is defined by neurological symptoms, retinal vasculopathy, accumulation of punctate cerebellar lesions and/or large mass-like lesions with surrounding vasogenic edema. Histopathology showed vasculopathy without inflammation. Treatments with immunosuppressants appeared largely ineffective. Imaging and pathology suggest a non-inflammatory small vessel vasculopathy as the primary pathology. InterpretationNOVA-FA is a recently identified condition that affects a subset of patients with FA and results in significant disability, including death. The etiology remains unknown, although the condition mimics features of the syndrome "retinal vasculopathy and cerebral leukodystrophy" which is due to dysfunction in DNA repair mechanisms. There is currently no known effective treatment. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSFanconi anemia is an inherited DNA-repair disorder, and only scattered case reports and small series have described an acquired neurological and ocular condition in a subset of these patients, and often presumed to be inflammatory. A consistent clinical-radiological definition, an understanding of the underlying mechanism, and evidence to guide treatment have been lacking. What this study addsThis series of six patients provides the most detailed clinical, radiological and pathological characterization of the syndrome to date, proposes the name Neuro-Ocular Vasculopathy Associated with Fanconi Anemia (NOVA-FA) with provisional diagnostic criteria, and shows that histopathology, CSF and serum biomarkers, infectious testing and treatment response together point to a non-inflammatory small vessel vasculopathy rather than a primary immune-mediated or infectious process, closely mirroring the DNA-repair disorder RVCL. How this study might affect research, practice or policyThe findings argue against reflexive immunosuppression, support earlier recognition of NOVA-FA through defined criteria, and reframe it as a DNA-repair-driven vasculopathy, motivating natural-history and mechanistic studies and the evaluation of vascular-targeted therapies as FA life expectancy rises and this phenotype becomes more common. Social Media Summary If PublishedNone of the co-authors have a X handle that we would like to be tagged. There are scant case reports about this emerging neurologic syndrome in patients with Fanconi Anemia. This study contains the most robust neurological phenotyping of these patients and explores in-depth evaluations for molecular presence of inflammation. Draft: A novel progressive neuro-ocular vasculopathy in Fanconi Anemia (NOVA-FA) presents with enhancing brain lesions and retinal changes. Likely due to microvascular DNA repair failure, not inflammation. #FanconiAnemia #Neurovascular #RareDisease
ER -