Phenotypical variability of cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL): Description of three cases in one family


DOI: https://dx.doi.org/10.18565/therapy.2023.5.94-103

Grigorieva V.N., Nesterova V.N., Ruina E.A., Sivograk A.A., Averina E.V.

1) Privolzhsky Research Medical University of the Ministry of Healthcare of Russia, Nizhny Novgorod; 2) N.A. Semashko Regional Clinical Hospital of Nizhny Novgorod
Abstract. Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) often causes diagnostic difficulties, which is facilitated by its clinical heterogeneity. The aim of the study was to describe three clinical cases of CADASIL in two adjacent generations of the same family in order to demonstrate the phenotypic variability of this pathology and increase medical alertness in that direction. Heterogeneity of CADASIL clinical manifestations in described clinical cases was manifested in a younger age of the symptoms’ onset in two sons of the female proband-patient; differences in the types and severity of strokes (mild lacunar in the mother and severe hemorrhagic in her eldest son), as well as the early onset and greater severity of cognitive disorder in youngest son. Common for all three patients was the absence of migraine, which is not typical for CADASIL in European geographical regions. This feature cannot be explained by the type of missense mutation p.Tyr189Cys found in the family in exon 4 of the NOTCH3 gene, since the same mutation was previously described by other authors in CADASIL patients with migraine. Medical alertness regarding CADASIL in young and middle-aged people with ischemic stroke and cognitive decline should take place even in cases where patients don’t have a headache.
Keywords: NOTCH3 gene mutations, phenotypic variability, stroke
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About the Autors

Vera N. Grigorieva, MD, professor, head of the Department of neurology, Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 Minina i Pozharskogo Sq. E-mail: vrgr@yandex.ru. ORCID: https://orcid.org/0000-0002-6256-3429
Valentina N. Nesterova, PhD in Medical Sciences, deputy chief physician for the regional vascular center, head of the Department for ACVA patients, N.A. Semashko Regional Clinical Hospital of Nizhny Novgorod. Address: 603126, Nizhny Novgorod, 190 Rodionova Str. E-mail: nesterova-78@mail.ru.
ORCID: https://orcid.org/0000-0002-2456-7971;
Ekaterina A. Ruina, PhD in Medical Sciences, associate professor of the Department of neurology, psychiatry and narcology of the Faculty of additional professional education, Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 Minina i Pozharskogo Sq. E-mail: ekaterina_ruina@mail.ru. ORCID: https://orcid.org/0000-0003-4595-2614
Anna A. Sivograk, resident physician of the Department of neurology, psychiatry and narcology of the Faculty of additional professional education, Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 Minina i Pozharskogo Sq. E-mail: sivograk.anna@mail.ru. ORCID: https://orcid.org/0009-0000-2975-6440
Ekaterina V. Averina, resident physician of the Department of neurology, psychiatry and narcology of the Faculty of additional professional education, Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 Minina i Pozharskogo Sq. E-mail: kovlyagina_96@mail.ru. ORCID: https://orcid.org/0009-0008-9644-4031


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