Objective: To explore the clinical presentations, pathological features, imaging manifestation and genetic mutation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Methods: A systematic study on the clinical manifestations, neuroimaging characteristics, pathology and molecular genetics was performed in the proband and 16 members of the family. An investigation on the hereditary pattern of the family tree of the proband was also conducted.
Results: The main clinical features including history of ischemic stroke attack, migraine, psychological disoders and dementia were noted. No risk factors of hypertension and arteriosclerosis were found. Pedigree maps of the index case were consistent with classical autosomal dominant inheritance. Subcortical multi-infarct lesions, leukoencephalopathy, O'Sullivan sign and "Herringbone pattern"shape sign were observed via cranial MRI analysis. By electron microscopy, skin biopsy indicated the characteristic deposition of granular osmiophilic material (GOM) on the basement of smooth muscle cells of arterioles in the proband. The mutation of C144Y in the fourth exon of notch 3 gene was revealed in three cases, including 1 patient with normal MRI.
Conclusion: The pedigree is diagnosed with CADASIL. The main cause can be attributed to a mutation of C144Y in the fourth exon of Notch 3 gene. The pedigree has enriched Chinese database of CADASIL.