Cadasil - genetic and ultrastructural diagnosis: case report

Abstract

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disorder which affects the cerebral vasculature due to mutations in the NOTCH 3 gene. The diagnosis may be established through genetic testing for detection of these mutations and/or by skin biopsy. We report a case of the disorder in a female patient, who presented recurrent transient ischemic attacks that evolved to progressive subcortical dementia. Neuroimaging disclosed extensive leukoaraiosis and lacunar infarcts. The genetic analysis for NOTCH 3 was confirmatory. The ultrastructural examination of the skin biopsy sample, initially negative, confirmed the presence of characteristic changes (presence of granular osmiophilic material inclusions [GOM]), after the analysis of new sections of the same specimen. The present findings indicate that negative findings on ultrastructural examinations of biopsy should not exclude the diagnosis of the disease and that further analyses of the sample may be necessary to detect the presence of GOM.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Presenting During the Postpartum Period as Postpartum Depression and Postpartum Psychosis

“…Genetic testing for NOTCH3 mutation remains the gold standard for diagnosis [ 14 ]. Skin biopsy for granular osmiophilic material (GOM) deposition using electron microscopic examination remains another useful way to diagnose CADASIL [ 14 ] although it is a possibility that at times skin biopsy may be negative [ 15 ].…”