| CADASIL (cerebral autosomal dominant | | | | might also have these health problems. |
| arteriopathy with subcortical infarcts and | | | | Genetic counseling is the process of providing |
| leukoencephalopathy) is the most common form | | | | individuals and families with information on the |
| of hereditary stroke disorder, and is thought to | | | | nature, inheritance, and implications of genetic |
| be caused by mutations of the Notch 3 gene on | | | | disorders to help them make informed medical |
| chromosome 19. The most common clinical | | | | and personal decisions. The following section deals |
| manifestations are migraine headaches and | | | | with genetic risk assessment and the use of |
| transient ischemic attacks or strokes, which | | | | family history and genetic testing to clarify genetic |
| usually occur between 40 and 50 years of age, | | | | status for family members. This section is not |
| although MRI is able to detect signs of the disease | | | | meant to address all personal, cultural, or ethical |
| years prior to clinical manifestation of disease. | | | | issues that individuals may face or to substitute |
| Cerebral autosomal arteriopathy with subcortical | | | | for consultation with a genetics professional. |
| infarcts and leukoencephalopathy (CADASIL) is | | | | The disease primarily affects small blood vessels |
| characterized by recurrent subcortical ischemic | | | | in the white matter of the brain. A mutation in the |
| strokes and dementia caused by mutations in the | | | | Notch3 gene alters the muscular walls in these |
| Notch3 gene. In Drosophila melanogaster, Notch | | | | small arteries. CADASIL is characterized by |
| signaling has a pleiotropic effect, affecting most | | | | migraine headaches and multiple strokes |
| tissues of the organism during development. | | | | progressing to dementia. Other symptoms include |
| Biochemical, histochemical, molecular, and genetic | | | | white matter lesions throughout the brain, |
| analyses were performed on muscle biopsy | | | | cognitive deterioration, seizures, vision problems, |
| specimens and fibroblasts obtained from patients | | | | and psychiatric problems such as severe |
| of a Spanish family with CADASIL. Additional | | | | depression and changes in behavior and |
| biochemical and molecular analyses of the | | | | personality. Individuals may also be at higher risk |
| N(55e11) mutant of D. melanogaster were | | | | of heart attack. Symptoms and disease onset |
| performed. | | | | vary widely, with signs typically appearing in the |
| An abnormality in the muscle cells surrounding | | | | mid-30s. Some individuals may not show signs of |
| these blood vessels (vascular smooth muscle | | | | the disease until later in life. |
| cells) gradually destroys these cells. The resulting | | | | There are several different methods of diagnosing |
| blood vessel damage can cause migraines and | | | | CADASIL. One of the most common methods is |
| other impairments of normal brain function. Later | | | | to take a skin biopsy, and examine it with a |
| in life, the damaged blood vessels can cause | | | | technique called electron microscopy, to look for |
| reduced blood flow to various tissues in the body | | | | the characteristic accumulations of granular |
| (ischemia). Although the severity of symptoms | | | | material (called granular osmiophilic material, or |
| varies among those affected, people with | | | | GOM) commonly seen in CADASIL. This can |
| CADASIL typically have more than one stroke in | | | | positively diagnose CADASIL, though a negative |
| their lifetime. Recurrent strokes can progressively | | | | result on this test does not necessarily mean that |
| damage the brain, causing loss of intellectual | | | | the disease is not present. Additionally, a skin |
| function (dementia). CADASIL is not associated | | | | biopsy can be tested for the accumulation of |
| with the common risk factors for stroke and | | | | Notch3, using a molecule that specifically detects |
| heart attack, such as high blood pressure and high | | | | this protein. |
| cholesterol, although some affected individuals | | | | |