OBJECTIVE: To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS: Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. CONCLUSIONS: Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.
OBJECTIVE: To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS: Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. CONCLUSIONS: Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.
Authors: A Bersano; M Kraemer; A Burlina; M Mancuso; J Finsterer; S Sacco; C Salvarani; L Caputi; H Chabriat; S Lesnik Oberstein; A Federico; E Tournier Lasserve; D Hunt; M Dichgans; M Arnold; S Debette; H S Markus Journal: J Neurol Date: 2020-04-21 Impact factor: 4.849
Authors: Dorothee Schoemaker; Yakeel T Quiroz; Heirangi Torrico-Teave; Joseph F Arboleda-Velasquez Journal: Neurosci Lett Date: 2019-01-08 Impact factor: 3.046