information about CADASIL Syndrome
Description
CADASIL is a rare genetic disorder that is characterized by migranes, headaches, and multiple strokes in adults and young adults, often without cardiovascular risk factors. CADASIL is caused by an autosomal dominant mutation in the NOTCH 3 receptor gene and results in damage of various small blood vessels, especially those within the brain. CADASIL stands for Cerebral Autosomal Dominant Arteriopathy Infarcts Leukoencephalopathy. Arteriopathy is the disease of the small arteries which are blood vessels that carry blood away from the heart, and infarcts is caused by a lack of oxygen to the brain when blood flow in the small arteries is blocked or abnormal resulting in tissue loss in the brain. Leukoencephalopathy is the destruction of the myelin, which protects and covers nerve fibres in the central nervous system.The age of onset, severity, specific symptoms and disease progression varies greatly from one person to another, even among members of the same family.
Prevalence
Prevalence of this disease remains unknown.
Causes
CADASIL is most often caused by mutations in the NOTCH3 gene, located located to 19p13.2-p13.1, which are mainly expressed in vascular smooth muscle cells. Over 90% of cases involve missense mutations which results in an alteration in numerical cysteine in the of the epidermal growth factor receptor encoding exons of NOTCH (exons 2-23). The mutated epidermal growth factor receptor contains 5 or 7 cysteine residues, instead of the regular 6, resulting in increased multimerisation of the mutated protein and accumulation of mutated NOTCH3 in the vascular wall.
Symptoms
CADASIL is characterized by migranes, headaches, and multiple strokes in adults and young adults, often without cardiovascular risk factors. Other possible symptoms include, mental impairment, seizures, cerebellar ataxia, lethargy, spasticity or involuntary muscle contractions, fever, drowsiness or coma, infarcts, and leukoencephalopathy.
Diagnosis & Diagnostic Tests
Diagnosis of CADASIL should be considered in patients with young-onset stroke, cognitive decline, ischemic changes on MRI (symmetrical white matter hyperintensities, subcortical infarctions, microbleeds), or a positive family history for stroke or dementia. Diagnosis can be confirmed through molecular analysis by the identification of a typical cysteine altering NOTCH3 mutation. An electron microscopy of a skin biopsy can reveal characteristic granular deposits or a immunohistochemical analysis can be used to show positive NOTCH3 staining of the vessel wall.
Prognosis
Prognosis is progressive and the earliest forms of CADASIL are the most severe. Prolonged periods of stability or even transient mild improvements lasting years are common. Most patients develop seizures (epilepsy) late in the illness that are easy to control. Life expectancy is reduced, though patients can live into their second or third decades.
CADASIL is a rare genetic disorder that is characterized by migranes, headaches, and multiple strokes in adults and young adults, often without cardiovascular risk factors. CADASIL is caused by an autosomal dominant mutation in the NOTCH 3 receptor gene and results in damage of various small blood vessels, especially those within the brain. CADASIL stands for Cerebral Autosomal Dominant Arteriopathy Infarcts Leukoencephalopathy. Arteriopathy is the disease of the small arteries which are blood vessels that carry blood away from the heart, and infarcts is caused by a lack of oxygen to the brain when blood flow in the small arteries is blocked or abnormal resulting in tissue loss in the brain. Leukoencephalopathy is the destruction of the myelin, which protects and covers nerve fibres in the central nervous system.The age of onset, severity, specific symptoms and disease progression varies greatly from one person to another, even among members of the same family.
Prevalence
Prevalence of this disease remains unknown.
Causes
CADASIL is most often caused by mutations in the NOTCH3 gene, located located to 19p13.2-p13.1, which are mainly expressed in vascular smooth muscle cells. Over 90% of cases involve missense mutations which results in an alteration in numerical cysteine in the of the epidermal growth factor receptor encoding exons of NOTCH (exons 2-23). The mutated epidermal growth factor receptor contains 5 or 7 cysteine residues, instead of the regular 6, resulting in increased multimerisation of the mutated protein and accumulation of mutated NOTCH3 in the vascular wall.
Symptoms
CADASIL is characterized by migranes, headaches, and multiple strokes in adults and young adults, often without cardiovascular risk factors. Other possible symptoms include, mental impairment, seizures, cerebellar ataxia, lethargy, spasticity or involuntary muscle contractions, fever, drowsiness or coma, infarcts, and leukoencephalopathy.
Diagnosis & Diagnostic Tests
Diagnosis of CADASIL should be considered in patients with young-onset stroke, cognitive decline, ischemic changes on MRI (symmetrical white matter hyperintensities, subcortical infarctions, microbleeds), or a positive family history for stroke or dementia. Diagnosis can be confirmed through molecular analysis by the identification of a typical cysteine altering NOTCH3 mutation. An electron microscopy of a skin biopsy can reveal characteristic granular deposits or a immunohistochemical analysis can be used to show positive NOTCH3 staining of the vessel wall.
Prognosis
Prognosis is progressive and the earliest forms of CADASIL are the most severe. Prolonged periods of stability or even transient mild improvements lasting years are common. Most patients develop seizures (epilepsy) late in the illness that are easy to control. Life expectancy is reduced, though patients can live into their second or third decades.