REVIEW article

Front. Neurol.

Sec. Neurogenetics

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1573052

Mechanistic Advances in Factors Influencing Phenotypic Variability in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Review

Provisionally accepted
  • 1Department of Neurology, Zhengzhou University People’s Hospital, Zhengzhou, Henan Province, China
  • 2Department of Neurology, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, China

The final, formatted version of the article will be published soon.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease caused by mutations in NOTCH3 and is the most common hereditary cerebral small-vessel disease in adults. The clinical manifestations of CADASIL include migraines, recurrent ischemic stroke, progressive cognitive deterioration, and psychiatric symptoms. The most prevalent and earliest imaging alterations in CADASIL are white matter hyperintensities in the periventricular white matter, temporal pole, external capsule, frontoparietal white matter, and other areas on magnetic resonance imaging. Despite the substantial variations in the clinical phenotypes and disease severity in patients with CADASIL, the specific mechanisms underlying these differences remain unclear. Exploring these underlying mechanisms is crucial for enhancing our understanding of CADASIL and offering insights into its early diagnosis and treatment. This review explores the advances in research on the molecular mechanisms that contribute to the variability in clinical phenotypes and disease severity among CADASIL patients with different mutations.

Keywords: CADASIL, Notch3, Granular osmiophilic material, Epidermal growth factor-like repeats, phenotype

Received: 10 Feb 2025; Accepted: 29 Apr 2025.

Copyright: © 2025 Zhao, Lu, Wang, Wang, Li, Sun, Shang, Jiang and Jiewen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zhang Jiewen, Department of Neurology, Zhengzhou University People’s Hospital, Zhengzhou, Henan Province, China

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