Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset hereditary syndrome characterized by recurrent TIAs and strokes, cognitive decline and dementia, migraine with aura (+/-40% of patients), and psychiatric disturbances (+/-30% of patients). Affected individuals have prominent signal abnormalities on brain MRI. Symmetrical white matter abnormalities are invariably seen and often small subcortical infarcts are also present. The extent of the MRI lesions increases with age, from subtle white matter abnormalities in the anterior temporal poles in the early 20 years to confluent white matter lesions with subcortical infarcts and microbleeds in the 6(th) decade. A typical arteriopathy with electron dense granular depositions in the media of small cerebral arteries underlies this disorder. These arterial lesions can be found, to a lesser extent, in extra-cerebral arteries such as skin arterioles. In 1996, the defective gene in CADASIL was discovered to be NOTCH3. NOTCH3 encodes a 300-kd transmembrane protein with a receptor and cell signal transduction function. Mutations are almost always missense mutations causing the loss or gain of a cysteine residue and are detected in over 90% of patients. How alterations in NOTCH3 lead to the CADASIL phenotype has yet to be elucidated.
Lesnik Oberstein
S A J
SA
Center for Human and Clinical Genetics, Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Haan
J
J
D000328:Adult; D000368:Aged; D000818:Animals; D046589:CADASIL / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002536:Cerebral Arteries / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch
C499374:NOTCH3 protein, human; C499373:Notch3 protein, mouse; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C073572:Notch4 protein, mouse