molecular investigation in 15 patients suspected to cadasil

cadasil (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by a history of migraine headaches (30%-40% of individuals), mid-adult (30s-60s) onset of cerebrovascular disease progressing to dementia, and diffuse white matter lesions and subcortical infarcts on neuroimaging. cadasil is an autosomal dominant disorder whose gene, notch3, is located on chromosome 19. the symptoms of cadasil are attributed to mutations in this gene. physiologically, the notch3 gene specifies cell fate in development. allelic variants of notch3 could also, although not yet demonstrated, be involved in other vascular conditions. in addition to the clinical workup for cadasil, genetic testing for this mutation can be used in familial or sporadic ischemic disorders of undetermined cause to assist in confirming a diagnosis. with up to 99% specificity, our labs cadasil dna sequencing test will detect approximately 85% of the mutations resulting in the phenotype of the disease. cadasil experts recommend that people under 65 with the following characteristics should be tested: depression, memory loss, behavior change, migraine, and/or stroke-like symptoms, such as recurrent stroke at a young age (<29 years old) when associated with prominent white matter disease/diffuse white matter hyperintensities on mri. • lack of significant vascular risk factors. • family history of migraine, young recurrent stroke, depression, cognitive impairment, or white matter changes. it is important to note that because there is no treatment for cadasil, a similar counseling protocol to huntingtons disease should be followed for presymptomatic patients. it is understood that presymptomatic genetic testing for cadasil can have potential benefit and clinical utility. often under appreciated, however, are the types of possible adverse outcomes and, the severity and duration of the problems. the american academy of neurology has published recommendations and practice guidelines to inform clinicians of issues surrounding the presymptomatic testing of individuals for disorders such as cadasil with the goal of optimizing benefits and minimizing adverse outcomes. we funded cadasil molecular genetic test in our lab in early 2008. we have checked eighteen patients since then (referred to our lab or diagnosed by dr. aryani). six of the eighteen cases were affected by cadasil and the others were normal. key note: the diagnosis should be considered not only in patients with recurrent small subcortical infarcts leading to dementia, but also in patients with transient ischemic attacks, migraine with aura, or severe mood disturbances, whenever mri reveals prominent signal abnormalities in the subcortical white matter and basal ganglia. clinical and mri investigations of family members are then crucial for the diagnosis, which can be confirmed by genetic analysis.