Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Youssef Awni; Bisharat Bishara; Bowirrat Abdalla

Volume : III, Issue : XII, December - 2014

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Youssef Awni, Bisharat Bishara, Bowirrat Abdalla

Abstract :

Cereal autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL, OMIM #125310) is a rare mid-adult onset monogenic form of hereditary cereal microangiopathy, caused by mutations in the NOTCH3 gene which lead to abnormal extracellular matrix accumulation of granular osmiophilic material (GOM) in the vicinity of vascular smooth muscle cells (VSMCs) causing degeneration and loss of VSMCs in small arteries and arterioles. Clinically the syndrome is manifested as migraine with aura, recurrent subcortical ischaemic events or strokes, subcortical vascular dementia and mood disorders. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. Diagnosis of CADASIL is established on the basis of results of genetic testing; skin biopsy and MRI. However, a genetic test is the gold standard to confirm the diagnosis and to identify a mutation in the underlying gene NOTCH3, which is caused by at least 170 mutations in the NOTCH3 gene at locus 19p13.1-13.26. Pathological test used to identify the GOM deposition around VSMCs examined by electron microscopy in skin biopsies is considered a specific diagnostic tool for CADASIL. In addition, imaging abnormalities in CADASIL evolve as the disease progresses: Typical MRI findings are T2 weighted hyperintensities in white matter and the capsula externa, Subcortical lacunar lesions and cereal microbleeds are seen. Only symptomatic treatment is obtainable for CADASIL. In this review we will discuss iefly the NOTCH subtypes and concentrate on NOTCH3 and its involvement in CADASIL syndrome.