"CADASIL coma" in an Italian homozygous CADASIL patient: comparison with clinical and MRI findings in age-matched heterozygous patients with the same G528C NOTCH3 mutation.

[cadasil]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ) is a genetic disorder caused by mutations in the NOTCH 3 gene , with a striking variability in phenotypic expression . To date , only two homozygous patients have been reported , with divergent phenotypic features . We describe an Italian CADASIL patient , homozygous for G 528 C mutation , in whom early manifestation of the disease was migraine , but whose clinical evolution was characterized by a reversible acute encephalopathy followed by full recovery ("CADASIL coma "). Clinical evaluation , MR scan , neuropsychological and neurophysiological investigation did not reveal substantial differences between our homozygous patient and her heterozygous relatives sharing the same mutation , or between our patient and a group of heterozygous individuals with the same mutation but from different families . Skin biopsy identified peculiar features in the homozygous patient , with cytoplasmic pseudoinclusions likely containing granular osmiophilic material (GOM ) in the vascular smooth muscle cells , but further studies are necessary to substantiate their possible relationships with CADASIL homozygosis . "CADASIL coma " did not seem to be specific of patient 's homozygosis , since it was observed in one of her heterozygous relatives , whereas its pathogenesis seems to be related to peculiar constellations of unknown predisposing factors . The present study demonstrated that CADASIL conforms to the classical definition of dominant diseases , according to which homozygotes and heterozygotes for a defect are phenotypically indistinguishable .

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