Clinical Information

There are many known monogenic conditions that increase an individual's risk for cerebrovascular accident or stroke. Most of these conditions are characterized by abnormal vascular development, abnormal intracranial blood flow, and weakening of the cerebral vessels. Depending on the pathophysiology of the associated condition, risk may be increased for ischemic stroke, hemorrhagic stroke, or both.(1)

Several vascular malformation syndromes are associated with an increased risk for stroke due to abnormalities in vascular development throughout the body.(1) Pulmonary arteriovenous malformations (AVM) are common features of autosomal dominant hereditary hemorrhagic telangiectasia and autosomal dominant capillary malformation-AVM. Pulmonary AVM increase the risk for ischemic stroke by allowing emboli to bypass the lungs and enter the cerebral vasculature.(1) Autosomal dominant familial cerebral cavernous malformation causes abnormal development of capillary channels within the brain and is associated with an increased risk for hemorrhagic stroke.(1,2)

Several monogenic connective tissue conditions leading to vascular fragility are associated with an increased risk for arterial dissection and ischemic stroke.(1) These conditions lead to defects impacting the structural integrity of blood vessels throughout the body resulting in a high risk for vessel rupture. This panel assesses several vascular fragility syndromes, including autosomal dominant vascular Ehlers-Danlos syndrome, autosomal dominant Loeys-Dietz syndrome, autosomal dominant familial aortic aneurysm and dissection, and autosomal recessive arterial tortuosity syndrome.(3-6)

Hereditary cerebral small vessel disease (SVD) is a group of conditions generally characterized by lacunar infarcts and white matter hyperintensities on magnetic resonance imaging and an increased risk for ischemic and/or hemorrhagic stroke.(1,7) The monogenic SVDs assessed on this panel include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant retinal vasculopathy with leukodystrophy, autosomal dominant COL4A1-associated SVD, and autosomal dominant COL4A2-associated SVD.(1, 7)

Moyamoya disease, a condition characterized by progressive narrowing of the blood vessels and an increased risk for ischemic stroke, can be inherited in an autosomal dominant manner. However, in most individuals, the genetic etiology (if any) remains unknown.(1,8)

Other conditions associated with increased risk for ischemic and hemorrhagic stroke assessed on this panel include X-linked Fabry disease, autosomal recessive homocystinuria due to variants in the CBS gene, and autosomal recessive adenosine deaminase 2 deficiency.(1,9)