Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Pantoni, Leonardo; Sarti, Cristina; Pescini, Francesca; Bianchi, Silvia; Bartolini, L.; Nencini, Patrizia; Basile, Anna; Lamassa, Maria; Kalaria, Raj N.; Dotti, Maria Teresa; Federico, Antonio; Inzitari, Domenico

doi:10.1111/j.1468-1331.2004.00915.x

Cited by 23 publications

(17 citation statements)

References 33 publications

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“…The presence of antiphospholipid antibodies has been reported in two unrelated female patients, suggesting that the diagnosis of CADASIL should not be disregarded in the presence of such autoantibody findings [10]. One patient carried the C406T mutation in exon 3 and the other carried the C1897T mutation in exon 11; the latter had initially received the diagnosis of antiphospholipid syndrome.…”

Section: Discussionmentioning

confidence: 99%

CADASIL and Autoimmunity: Coexistence in a Family with the R169C Mutation at Exon 4 of the NOTCH3 Gene

et al. 2014

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Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by mutations of the NOTCH3 gene, which result in degeneration of vascular smooth muscle cells, arteriolar stenosis, and impaired cerebral blood flow. For clinicians this is the commonest hereditary adult-onset condition causing stroke and vascular dementia at middle age.Atypical phenotypes have been recognized, and the disease is probably underdiagnosed in the wider stroke population. Coexistence of autoimmunity is atypical and has been described only in occasional patients. Methods: Three members of a Greek family from the island of Lesvos of North East Greece were evaluated. The patients come from a four-generation family in which there were at least seven members with clinical data suggestive of CADASIL. We describe here the clinical, imaging and biochemical findings in this family with R169C mutation at exon 4 and presenting additional clinical and biochemical findings suggestive of autoimmune disorder. DNA was extracted from whole blood using standard procedures for sequencing. Results: Three affected members of this family carried the R169C. In a phenotypic analysis of affected individuals from four generations with CADASIL, the disease was characterized by migraine attacks, recurrent subcortical infarcts, and cognitive decline with typical anterior temporal lobe white matter lesions. At least 3 mutation carriers from two generations had increased antinuclear antibody (ANA) titers and various combinations of rash, joint pains, photosensitivity, and renal involvement. Conclusion: This is a rare description of the coexistence of autoimmunity in CADASIL patients with possible worsening clinical effects. The study extends the spectrum of atypical presentation of CADASIL. The coexistence of autoimmunity does not necessarily exclude CADASIL, but may cause an additional diagnostic and therapeutic challenge. This autoimmune disorder may have increased the severity of the disease and, additionally, may be related to the pathogenetic mechanisms of CADASIL. It is possible that the NOTCH3 mutation alone is not enough to trigger autoimmunity since, in the case of our family, the R169C mutation has already been described in other families with no evidence of coexistent autoimmunity. Other genetic or environmental factors or interactions and/or common pathways between the vascular and immune systems are probably co-operating. Further, prospective studies are needed to clarify the prevalence and types of autoimmune disorders present in CADASIL families.

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Section: Discussionmentioning

confidence: 99%

CADASIL and Autoimmunity: Coexistence in a Family with the R169C Mutation at Exon 4 of the NOTCH3 Gene

et al. 2014

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“…Pathologic findings in I-2 and II-2 were different from those in Parkinson's disease and Alzheimer's disease. Fourth, periventricular white matter change in the temporal horn is one of the other possible causes of the psychiatric symptoms [21], or CADASIL patients with a vascular risk factors are reported to show symptoms related to cortical involvement [22]. Furthermore, no family member was treated with hallucinogenic drugs [14].…”

Section: Discussionmentioning

confidence: 99%

CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations

Nakamura

Watanabe

Hirayama

et al. 2005

Journal of the Neurological Sciences

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“…Lp(a) levels were measured for various reasons in eight members of these CADASIL families by the same laboratory, and found elevated in seven (Table 1) (one patient already reported) [2]. Patients had various association of other vascular risk factors.…”

Section: Dear Sirsmentioning

confidence: 98%

High lipoprotein(a) serum levels in three CADASIL families

et al. 2011

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Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Cited by 23 publications

References 33 publications

CADASIL and Autoimmunity: Coexistence in a Family with the R169C Mutation at Exon 4 of the <b><i>NOTCH3</i></b> Gene

CADASIL and Autoimmunity: Coexistence in a Family with the R169C Mutation at Exon 4 of the <b><i>NOTCH3</i></b> Gene

CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations

High lipoprotein(a) serum levels in three CADASIL families

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