Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I--A review of clinical, radiologic and genetic aspects.

[hereditary cerebral hemorrhage with amyloidosis]

Hereditary cerebral hemorrhage with amyloidosis -Dutch type (HCHWA-D ) is an autosomal dominant disease caused by deposition of beta -amyloid in the leptomeningeal arteries and cortical arterioles , in addition to preamyloid deposits and amyloid plaques in the brain parenchyma . The disease is due to a point mutation at codon 693 of the amyloid precursor protein (beta PP ) gene at chromosome 21 . Since this point mutation is diagnostic for HCHWA-D , presymptomatic testing is feasible and offered , together with genetic counselling and psychological support , to subjects at risk . HCHWA-D is clinically characterized by recurrent strokes , in addition to dementia , which can occur after the first stroke but also preceding it . Radiological studies revealed focal lesions (hemorrhages , hemorrhagic and non-hemorrhagic infarctions ) and diffuse white matter damage . Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke . The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo . The characteristic pathological abnormalities and its implications for Alzheimer 's disease will be discussed in Part II of this article .