CADASIL
Communication of a Uruguayan family with clinical, imaging, pathological and molecular genetic definition
Keywords:
CADASIL, EXONS, NOTCH RECEIVERS, MUTATIONAbstract
Introduction: CADASIL syndrome (Cerebral Dominant Arteriopathy with Subcortical Infarcts and Leukoencephlopathy), the most common form of hereditary stroke disorder is a nonamyloid, non-atheromatous microangiopathy. Main clinical features are found in the brain. The disease may be diagnosed by clinical findings, images and genetic molecular criteria.
Methods: an anatomopathological analysis through a skin and muscle biopsy and molecular study was performed on three members of the same family diagnosed with CADASIL.
Results: clinical, paraclinical, neurological and ultrastructural skin biopsy study’s findings were consistent with CADASIL. Notch3 sequence exonal analysis (2,3,4,5,8,11,20,23) suggested heterocigotic mutations in exon 5, not previously described in literature.
Conclusions: we stress the importance of early diagnosis of this disease and the molecular definition that enables genetic counselling to all members of the family and, potentially, prenatal diagnosis of the disease.
References
(1) Sourander P, Walinder J. Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease. Acta Neurophatol 1977; 39(3): 247-54.
(2) Sonninen V, Savontaus ML. Hereditary multi-infarct dementia. Eur Neurol 1987; 27(4): 209-15.
(3) Verin M, Rolland Y, Landgraf F, Chabriat H, Bompais B, Michel A, et al. New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature. J Neurol Neurosurg Psychiatry 1995; 59(6): 579-85.
(4) Glusker P, Horoupian DS, Lane B. Familial arteriopathic leukoencephalopathy: imaging and neuropathologic findings. AJNR Am J Neuroradiol 1998; 19(3): 469-75.
(5) Kalimo H, Viitanen M, Amberla K, Juvonen V, Marttila R, Pöyhönen M, et al. CADASIL: hereditary disease of arteries causing brain infarcts and dementia. Neuropathol Appl Neurobiol 1999; 25(4): 257-65.
(6) Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383(6602): 707-10.
(7) Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 1993; 3(3): 256-9.
(8) Ruchoux MM, Guerouaou D, Vandenhaute B, Pruvo JP, Vermersch P, Leys D. Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol 1995; 89(6): 500-12.
(9) Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategis in CADASIL. Neurology 2002; 59(8): 1134-8.
(10) Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier-Lasserve E. Presence of ultraestructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 1994; 25(11): 2291-2.
(11) Iglesias M, Jimeno M, García M, Mon D, Roquer J, Alameda F, et al. CADASIL electron-dense deposits are not osmiophilic. Report of a non-familial case. ULTRAPATH, 12. Conference on Diagnostic Electron Microscopy with Surgical, Clinical, and Molecular Pathology Correlations Barcelona, Spain July 11-16, 2004.
(12) Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001; 358(9298): 2049-51.
(13) Ishida C, Sakajiri K, Yoshita M, Joutel A, Cave-Riant F, Yamada M. CADASIL with a novel mutation in exon 7 of NOTCH3 (C388Y). Intern Med 2006; 45(16): 981-5.
(14) Bancroft J, Stevens A. Theory and practice of histological techniques. 2 ed. New York: Churchill Livingstone, 1982.
(15) Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997; 350(9090): 1511-5.
(16) Bousser M, Tournier-Lasserve E. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoence-phalopathy: from stroke to vessel wall physiology. J Neurol Neurosurg Psychiatry 2001; 70(3): 285-7.
(17) Yanagawa S, Ito N, Arima K, Ikeda S. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Neurology 2002; 58(5): 817-20.
(18) Peters N, Opherk C, Bergmann T, Castro M, Herzog J, Dichgans M. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol 2005; 62(7): 1091-4.
(19) Joutel A, Monet M, Domenga V, Riant F, Tournier-Lasserve E. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect jaggedl binding and Notch3 activity via the RBP/JK signalling pathway. Am J Hum Genet 2004; 74(2): 338-47.
(20) Vikelis M, Papatriantafyllou J, Karageorgiou CE. A novel CADASIL causing mutation in a stroke patient. Swiss Med Wkly 2007, 137(21-22): 323-5.
(2) Sonninen V, Savontaus ML. Hereditary multi-infarct dementia. Eur Neurol 1987; 27(4): 209-15.
(3) Verin M, Rolland Y, Landgraf F, Chabriat H, Bompais B, Michel A, et al. New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature. J Neurol Neurosurg Psychiatry 1995; 59(6): 579-85.
(4) Glusker P, Horoupian DS, Lane B. Familial arteriopathic leukoencephalopathy: imaging and neuropathologic findings. AJNR Am J Neuroradiol 1998; 19(3): 469-75.
(5) Kalimo H, Viitanen M, Amberla K, Juvonen V, Marttila R, Pöyhönen M, et al. CADASIL: hereditary disease of arteries causing brain infarcts and dementia. Neuropathol Appl Neurobiol 1999; 25(4): 257-65.
(6) Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383(6602): 707-10.
(7) Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 1993; 3(3): 256-9.
(8) Ruchoux MM, Guerouaou D, Vandenhaute B, Pruvo JP, Vermersch P, Leys D. Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol 1995; 89(6): 500-12.
(9) Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategis in CADASIL. Neurology 2002; 59(8): 1134-8.
(10) Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier-Lasserve E. Presence of ultraestructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 1994; 25(11): 2291-2.
(11) Iglesias M, Jimeno M, García M, Mon D, Roquer J, Alameda F, et al. CADASIL electron-dense deposits are not osmiophilic. Report of a non-familial case. ULTRAPATH, 12. Conference on Diagnostic Electron Microscopy with Surgical, Clinical, and Molecular Pathology Correlations Barcelona, Spain July 11-16, 2004.
(12) Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001; 358(9298): 2049-51.
(13) Ishida C, Sakajiri K, Yoshita M, Joutel A, Cave-Riant F, Yamada M. CADASIL with a novel mutation in exon 7 of NOTCH3 (C388Y). Intern Med 2006; 45(16): 981-5.
(14) Bancroft J, Stevens A. Theory and practice of histological techniques. 2 ed. New York: Churchill Livingstone, 1982.
(15) Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997; 350(9090): 1511-5.
(16) Bousser M, Tournier-Lasserve E. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoence-phalopathy: from stroke to vessel wall physiology. J Neurol Neurosurg Psychiatry 2001; 70(3): 285-7.
(17) Yanagawa S, Ito N, Arima K, Ikeda S. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Neurology 2002; 58(5): 817-20.
(18) Peters N, Opherk C, Bergmann T, Castro M, Herzog J, Dichgans M. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol 2005; 62(7): 1091-4.
(19) Joutel A, Monet M, Domenga V, Riant F, Tournier-Lasserve E. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect jaggedl binding and Notch3 activity via the RBP/JK signalling pathway. Am J Hum Genet 2004; 74(2): 338-47.
(20) Vikelis M, Papatriantafyllou J, Karageorgiou CE. A novel CADASIL causing mutation in a stroke patient. Swiss Med Wkly 2007, 137(21-22): 323-5.
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Published
2008-03-31
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1.
Vaglio A, Ferreira M, Panuncio AL, Castagnola MA, Pebet M, De la Peña S, et al. CADASIL: Communication of a Uruguayan family with clinical, imaging, pathological and molecular genetic definition. Rev. Méd. Urug. [Internet]. 2008 Mar. 31 [cited 2024 Sep. 16];24(1):24-31. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/591
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