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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)

MedGen UID:
199687
•Concept ID:
C0751587
•
Disease or Syndrome
Synonyms: CADASIL; CASIL; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
SNOMED CT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (390936003)
 
Gene (location): NOTCH3 (19p13.12)
Related gene: HTRA1
 
Monarch Initiative: MONDO:0007432
OMIM®: 125310
OMIM® Phenotypic series: PS125310

Disease characteristics

Excerpted from the GeneReview: CADASIL
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by mid-adult onset of recurrent ischemic stroke, cognitive decline progressing to dementia, a history of migraine with aura, mood disturbance, apathy, and diffuse white matter lesions and subcortical infarcts on neuroimaging. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Remco J Hack  |  Julie Rutten  |  Saskia AJ Lesnik Oberstein   view full author information

Additional description

From OMIM
Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive disorder of the small arterial vessels of the brain manifest by migraine, strokes, and white matter lesions, with resultant cognitive impairment in some patients (review by Kalimo et al., 1999). Genetic Heterogeneity of Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CADASIL2 (616779) is caused by mutation in the HTRA1 gene (602194) on chromosome 10q26.  http://www.omim.org/entry/125310

Professional guidelines

PubMed

Genotype and Phenotype Differences in CADASIL from an Asian Perspective.
Kim Y, Bae JS, Lee JY, Song HK, Lee JH, Lee M, Kim C, Lee SH
Int J Mol Sci 2022 Sep 29;23(19) doi: 10.3390/ijms231911506. PMID: 36232798Free PMC Article
Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology.
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Genetic testing and counseling in the diagnosis and management of young-onset dementias.
Goldman JS
Psychiatr Clin North Am 2015 Jun;38(2):295-308. Epub 2015 Mar 18 doi: 10.1016/j.psc.2015.01.008. PMID: 25998117

Recent clinical studies

Etiology

Massive Microbleeds in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.
Ling C, Bai L, Guo Y, Yuan Y, Peng Q
Stroke 2023 Dec;54(12):e496-e497. Epub 2023 Oct 16 doi: 10.1161/STROKEAHA.123.045011. PMID: 37842780
Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts And Leukoencephalopathy Hidden by Another Stroke.
Yoon JY, Klein JP
Stroke 2022 Sep;53(9):e422-e423. Epub 2022 Jul 15 doi: 10.1161/STROKEAHA.122.039829. PMID: 35862215
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
CADASIL: new advances in basic science and clinical perspectives.
Ferrante EA, Cudrici CD, Boehm M
Curr Opin Hematol 2019 May;26(3):193-198. doi: 10.1097/MOH.0000000000000497. PMID: 30855338Free PMC Article
Migraine and stroke.
Zhang Y, Parikh A, Qian S
Stroke Vasc Neurol 2017 Sep;2(3):160-167. Epub 2017 May 29 doi: 10.1136/svn-2017-000077. PMID: 28989805Free PMC Article

Diagnosis

CADASIL: A NOTCH3-associated cerebral small vessel disease.
Yuan L, Chen X, Jankovic J, Deng H
J Adv Res 2024 Dec;66:223-235. Epub 2024 Jan 2 doi: 10.1016/j.jare.2024.01.001. PMID: 38176524Free PMC Article
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
CADASIL: new advances in basic science and clinical perspectives.
Ferrante EA, Cudrici CD, Boehm M
Curr Opin Hematol 2019 May;26(3):193-198. doi: 10.1097/MOH.0000000000000497. PMID: 30855338Free PMC Article
Migraine and stroke.
Zhang Y, Parikh A, Qian S
Stroke Vasc Neurol 2017 Sep;2(3):160-167. Epub 2017 May 29 doi: 10.1136/svn-2017-000077. PMID: 28989805Free PMC Article
White Matter Diseases with Radiologic-Pathologic Correlation.
Sarbu N, Shih RY, Jones RV, Horkayne-Szakaly I, Oleaga L, Smirniotopoulos JG
Radiographics 2016 Sep-Oct;36(5):1426-47. doi: 10.1148/rg.2016160031. PMID: 27618323

Therapy

Intracerebral Hemorrhage in Autosomal Dominant Cerebral Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.
Hu F, Xie W, Fan M, Wang Y, Xu S, Qiu W, Yang T, Lv H, Huang H, Wu Y, Fu Y, Cai B
Eur J Neurol 2025 Mar;32(3):e70100. doi: 10.1111/ene.70100. PMID: 40067051
Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial.
Kopczak A, Stringer MS, van den Brink H, Kerkhofs D, Blair GW, van Dinther M, Reyes CA, Garcia DJ, Onkenhout L, Wartolowska KA, Thrippleton MJ, Kampaite A, Duering M, Staals J, Lesnik-Oberstein S, Muir KW, Middeke M, Norrving B, Bousser MG, Mansmann U, Rothwell PM, Doubal FN, van Oostenbrugge R, Biessels GJ, Webb AJS, Wardlaw JM, Dichgans M; TREAT-SVDs collaborators
Lancet Neurol 2023 Nov;22(11):991-1004. doi: 10.1016/S1474-4422(23)00293-4. PMID: 37863608
Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Syndrome, a Central Nervous System Vasculitis Mimic.
Maheswaranathan M, Buckley AF, Cutler AB, Criscione-Schreiber L, Shah A
Arthritis Rheumatol 2021 Dec;73(12):2239. Epub 2021 Oct 26 doi: 10.1002/art.41922. PMID: 34279052
Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis.
Battle CE, Abdul-Rahim AH, Shenkin SD, Hewitt J, Quinn TJ
Cochrane Database Syst Rev 2021 Feb 22;2(2):CD013306. doi: 10.1002/14651858.CD013306.pub2. PMID: 33704781Free PMC Article
Acute Stroke as the Presenting Symptom of SARS-CoV-2 Infection in a Young Patient with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
Trifan G, Hillmann M, Testai FD
J Stroke Cerebrovasc Dis 2020 Oct;29(10):105167. Epub 2020 Jul 20 doi: 10.1016/j.jstrokecerebrovasdis.2020.105167. PMID: 32912545Free PMC Article

Prognosis

Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.
Ishiyama H, Kim H, Saito S, Takeda S, Takegami M, Yamamoto Y, Abe S, Nakazawa S, Tanaka T, Washida K, Morita Y, Oh ST, Jung HJ, Choi JC, Nakaoku Y, Nakahara J, Koga M, Toyoda K, Amemiya K, Ikeda Y, Hatakeyama K, Mizuta I, Mizuno T, Kim KK, Ihara M
Ann Neurol 2024 Jun;95(6):1040-1054. Epub 2024 Mar 23 doi: 10.1002/ana.26916. PMID: 38520151
CADASIL: A NOTCH3-associated cerebral small vessel disease.
Yuan L, Chen X, Jankovic J, Deng H
J Adv Res 2024 Dec;66:223-235. Epub 2024 Jan 2 doi: 10.1016/j.jare.2024.01.001. PMID: 38176524Free PMC Article
Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease.
Li Y, Ying Y, Yao T, Jia X, Liang H, Tang W, Jia X, Song H, Shao X, Wang DJJ, Wang C, Cheng X, Yang Q
Brain 2023 Jul 3;146(7):3079-3087. doi: 10.1093/brain/awac500. PMID: 36625892Free PMC Article
Migraine and stroke.
Zhang Y, Parikh A, Qian S
Stroke Vasc Neurol 2017 Sep;2(3):160-167. Epub 2017 May 29 doi: 10.1136/svn-2017-000077. PMID: 28989805Free PMC Article
Stroke and cognition.
Kalaria RN, Ballard C
Curr Atheroscler Rep 2001 Jul;3(4):334-9. doi: 10.1007/s11883-001-0028-5. PMID: 11389800

Clinical prediction guides

Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases.
Ying Y, Li Y, Yao T, Shao X, Tang W, Montagne A, Chabriat H, Wang DJJ, Wang C, Yang Q, Cheng X
Alzheimers Dement 2024 Jul;20(7):4527-4539. Epub 2024 May 24 doi: 10.1002/alz.13874. PMID: 38787758Free PMC Article
CADASIL: A NOTCH3-associated cerebral small vessel disease.
Yuan L, Chen X, Jankovic J, Deng H
J Adv Res 2024 Dec;66:223-235. Epub 2024 Jan 2 doi: 10.1016/j.jare.2024.01.001. PMID: 38176524Free PMC Article
Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease.
Li Y, Ying Y, Yao T, Jia X, Liang H, Tang W, Jia X, Song H, Shao X, Wang DJJ, Wang C, Cheng X, Yang Q
Brain 2023 Jul 3;146(7):3079-3087. doi: 10.1093/brain/awac500. PMID: 36625892Free PMC Article
Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology.
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
CADASIL: new advances in basic science and clinical perspectives.
Ferrante EA, Cudrici CD, Boehm M
Curr Opin Hematol 2019 May;26(3):193-198. doi: 10.1097/MOH.0000000000000497. PMID: 30855338Free PMC Article

Recent systematic reviews

Phenotypes Associated with NOTCH3 Cysteine-Sparing Mutations in Patients with Clinical Suspicion of CADASIL: A Systematic Review.
Cao Y, Zhang DD, Han F, Jiang N, Yao M, Zhu YC
Int J Mol Sci 2024 Aug 13;25(16) doi: 10.3390/ijms25168796. PMID: 39201482Free PMC Article
Contribution of "Omic" Studies to the Understanding of Cadasil. A Systematic Review.
Muiño E, Fernández-Cadenas I, Arboix A
Int J Mol Sci 2021 Jul 8;22(14) doi: 10.3390/ijms22147357. PMID: 34298974Free PMC Article
Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis.
Battle CE, Abdul-Rahim AH, Shenkin SD, Hewitt J, Quinn TJ
Cochrane Database Syst Rev 2021 Feb 22;2(2):CD013306. doi: 10.1002/14651858.CD013306.pub2. PMID: 33704781Free PMC Article
Intracerebral hemorrhage in CADASIL.
Palazzo P, Le Guyader G, Neau JP
Rev Neurol (Paris) 2021 Apr;177(4):422-430. Epub 2021 Jan 19 doi: 10.1016/j.neurol.2020.10.009. PMID: 33478738
l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.
Karlsson WK, Sørensen CG, Kruuse C
Clin Exp Pharmacol Physiol 2017 Jan;44(1):13-20. doi: 10.1111/1440-1681.12679. PMID: 27704594

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