TY - JOUR
T1 - "CADASIL coma" in an Italian homozygous CADASIL patient
T2 - Comparison with clinical and MRI findings in age-matched heterozygous patients with the same G528C NOTCH3 mutation
AU - Ragno, Michele
AU - Pianese, Luigi
AU - Morroni, Manrico
AU - Cacchiò, Gabriella
AU - Manca, Antonio
AU - Di Marzio, Fabio
AU - Silvestri, Serena
AU - Miceli, Cristina
AU - Scarcella, Maria
AU - Onofrj, Marco
AU - Trojano, Luigi
PY - 2013/11
Y1 - 2013/11
N2 - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by mutations in the NOTCH3 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 G528C 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.
AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by mutations in the NOTCH3 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 G528C 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.
KW - Autosomal dominance
KW - CADASIL
KW - Homozygosis
KW - Migraine
KW - Stroke
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U2 - 10.1007/s10072-013-1418-5
DO - 10.1007/s10072-013-1418-5
M3 - Article
C2 - 23572112
AN - SCOPUS:84888299678
VL - 34
SP - 1947
EP - 1953
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
IS - 11
ER -