elastin and Cerebral-Arterial-Diseases

Williams syndrome, a rare genetic disorder with a striking neurobehavioral profile characterized by extreme sociability and impaired visuospatial construction abilities, is caused by a hemideletion that includes the elastin gene, resulting in frequent supravavular aortic stenosis and other stenotic arterial lesions. Strokes have been reported in Williams syndrome. Although the extracranial carotid artery has been studied in a sample of patients with Williams syndrome, proximal intracranial arteries have not.. Using MRA, we studied the intracranial vessels in 27 participants: 14 patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 ± 9.1; 43% women) and 13 healthy control participants with similar age and sex distribution (age range, 22-52 years; mean age, 33.4 ± 7.6; 46% women). All participants with Williams syndrome had hemideletions of the elastin gene. Blinded to group allocation or to any other clinical data, a neuroradiologist determined the presence of intracranial vascular changes in the 2 groups.. The Williams syndrome group and the healthy control group had similar patency of the proximal intracranial arteries, including the internal carotid and vertebral arteries; basilar artery; and stem and proximal branches of the anterior cerebral artery, MCA, and posterior cerebral arteries. The postcommunicating segment of the anterior cerebral artery was longer in the Williams syndrome group.. Despite the elastin haploinsufficiency, the proximal intracranial arteries in Williams syndrome preserve normal patency.

Topics: Adolescent; Adult; Cerebral Arterial Diseases; Cerebral Arteries; Elastin; Gene Deletion; Genetic Predisposition to Disease; Humans; Magnetic Resonance Angiography; Reproducibility of Results; Sensitivity and Specificity; Vascular Patency; Williams Syndrome; Young Adult

This study was performed on a family of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) subjects. Neuropathological alterations of small arteries consisting in thickening, reduplication and fragmentation of the internal elastic lamella, and granular periodic acid-Schiff-positive material deposited in the arterial media were demonstrated in 1 autopsy case by histochemistry and electron microscopy. This material reacted with a monoclonal antibody anti-elastin (aE), as demonstrated by immunohistochemistry and immunoelectron microscopy. Significant increases of aE-immunoreactivity and elastin mRNA expression were found in cultured skin fibroblasts from 5 family members genetically affected by CADASIL, but not genetically and clinically healthy members. These results suggest that alterations of the elastic apparatus are associated with CADASIL genotype and related to the clinical expression of the disease.

Topics: Adult; Analysis of Variance; Biopsy, Needle; Brain; Cells, Cultured; Cerebral Arterial Diseases; Cerebral Arteries; Cerebral Infarction; Collagen; Elastin; Female; Fibroblasts; Fibronectins; Follow-Up Studies; Humans; Immunohistochemistry; Ischemic Attack, Transient; Leukoencephalopathy, Progressive Multifocal; Male; Microscopy, Electron; Middle Aged; Reference Values; RNA, Messenger; Skin; Syndrome

We describe an otherwise healthy 2-year-old patient with Williams syndrome who had a stroke as a result of intracranial multivessel focal and segmental stenotic disease. The diagnosis of Williams syndrome was confirmed by elastin gene deletion testing. Combined magnetic resonance imaging and magnetic resonance angiography, and transcranial Doppler flow studies, were used in diagnosing and monitoring the course of the disease.

Topics: Brain Ischemia; Cerebral Arterial Diseases; Constriction, Pathologic; Elastin; Gene Deletion; Humans; Infant; Infant, Newborn; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Ultrasonography, Doppler, Transcranial; Vascular Diseases