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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

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
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects.
Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT, Duering M, Jouvent E, Korczyn AD, Lesnik-Oberstein SA, Malandrini A, Markus HS, Pantoni L, Penco S, Rufa A, Sinanović O, Stojanov D, Federico A
BMC Med 2017 Feb 24;15(1):41. doi: 10.1186/s12916-017-0778-8. PMID: 28231783Free PMC Article
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

Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.
Walsh J, Tozer DJ, Sari H, Hong YT, Drazyk A, Williams G, Shah NJ, O'Brien JT, Aigbirhio FI, Rosenberg G, Fryer TD, Markus HS
Brain 2021 Jun 22;144(5):1361-1371. doi: 10.1093/brain/awab003. PMID: 34000009Free 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
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

Monogenic Causes of Strokes.
Chojdak-Łukasiewicz J, Dziadkowiak E, Budrewicz S
Genes (Basel) 2021 Nov 23;12(12) doi: 10.3390/genes12121855. PMID: 34946804Free 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
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
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects.
Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT, Duering M, Jouvent E, Korczyn AD, Lesnik-Oberstein SA, Malandrini A, Markus HS, Pantoni L, Penco S, Rufa A, Sinanović O, Stojanov D, Federico A
BMC Med 2017 Feb 24;15(1):41. doi: 10.1186/s12916-017-0778-8. PMID: 28231783Free 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

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 Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Prevalence, Clinical and Neuroimaging Features and Risk Factors.
Liao YC, Hu YC, Chung CP, Wang YF, Guo YC, Tsai YS, Lee YC
Stroke 2021 Mar;52(3):985-993. Epub 2021 Feb 4 doi: 10.1161/STROKEAHA.120.030664. PMID: 33535780
CADASIL from Bench to Bedside: Disease Models and Novel Therapeutic Approaches.
Manini A, Pantoni L
Mol Neurobiol 2021 Jun;58(6):2558-2573. Epub 2021 Jan 19 doi: 10.1007/s12035-021-02282-4. PMID: 33464533Free PMC Article
Multi-shell Diffusion MRI Models for White Matter Characterization in Cerebral Small Vessel Disease.
Konieczny MJ, Dewenter A, Ter Telgte A, Gesierich B, Wiegertjes K, Finsterwalder S, Kopczak A, Hübner M, Malik R, Tuladhar AM, Marques JP, Norris DG, Koch A, Dietrich O, Ewers M, Schmidt R, de Leeuw FE, Duering M
Neurology 2021 Feb 2;96(5):e698-e708. Epub 2020 Nov 16 doi: 10.1212/WNL.0000000000011213. PMID: 33199431
Nucleic Acid Therapies for Ischemic Stroke.
Henninger N, Mayasi Y
Neurotherapeutics 2019 Apr;16(2):299-313. doi: 10.1007/s13311-019-00710-x. PMID: 30635869Free PMC Article

Prognosis

Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa.
Akinyemi RO, Owolabi MO, Ihara M, Damasceno A, Ogunniyi A, Dotchin C, Paddick SM, Ogeng'o J, Walker R, Kalaria RN
Brain Res Bull 2019 Feb;145:97-108. Epub 2018 May 25 doi: 10.1016/j.brainresbull.2018.05.018. PMID: 29807146Free 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
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification.
Fukutake T
J Stroke Cerebrovasc Dis 2011 Mar-Apr;20(2):85-93. Epub 2011 Jan 7 doi: 10.1016/j.jstrokecerebrovasdis.2010.11.008. PMID: 21215656
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Guidetti D, Casali B, Mazzei RL, Dotti MT
Clin Exp Hypertens 2006 Apr-May;28(3-4):271-7. doi: 10.1080/10641960600549223. PMID: 16833034
Cerebral microhemorrhage.
Viswanathan A, Chabriat H
Stroke 2006 Feb;37(2):550-5. Epub 2006 Jan 5 doi: 10.1161/01.STR.0000199847.96188.12. PMID: 16397165

Clinical prediction guides

Cerebral Microbleed Burdens in Specific Brain Regions Are Associated With Disease Severity of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.
Chung CP, Chen JW, Chang FC, Li WC, Lee YC, Chen LF, Liao YC
J Am Heart Assoc 2020 Jul 7;9(13):e016233. Epub 2020 Jun 17 doi: 10.1161/JAHA.120.016233. PMID: 32552418Free 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
Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa.
Akinyemi RO, Owolabi MO, Ihara M, Damasceno A, Ogunniyi A, Dotchin C, Paddick SM, Ogeng'o J, Walker R, Kalaria RN
Brain Res Bull 2019 Feb;145:97-108. Epub 2018 May 25 doi: 10.1016/j.brainresbull.2018.05.018. PMID: 29807146Free PMC Article
Cerebral microhemorrhage.
Viswanathan A, Chabriat H
Stroke 2006 Feb;37(2):550-5. Epub 2006 Jan 5 doi: 10.1161/01.STR.0000199847.96188.12. PMID: 16397165

Recent systematic reviews

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
Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL.
Muiño E, Gallego-Fabrega C, Cullell N, Carrera C, Torres N, Krupinski J, Roquer J, Montaner J, Fernández-Cadenas I
Int J Mol Sci 2017 Sep 13;18(9) doi: 10.3390/ijms18091964. PMID: 28902129Free PMC Article
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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