This Article Full Text Full Text (PDF) All Versions of this Article: 40/6/2215    most recent STROKEAHA.108.528661v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mykkänen, K. Articles by Viitanen, M. Search for Related Content PubMed PubMed Citation Articles by Mykkänen, K. Articles by Viitanen, M. Related Collections Other Vascular biology

(Stroke. 2009;40:2215.)
© 2009 American Heart Association, Inc.

Research Letters

Different Clinical Phenotypes in Monozygotic CADASIL Twins With a Novel NOTCH3 Mutation

Kati Mykkänen, MSc; Maija Junna, MSc; Kaarina Amberla, MSc; Lena Bronge, MD; Helena Kääriäinen, MD; Minna Pöyhönen, MD; Hannu Kalimo, MD Matti Viitanen, MD

From the Department of Medical Biochemistry and Genetics (K.M., M.J., H. Kääriäinen), University of Turku, Finland; the Division of Clinical Geriatrics (K.A., M.V.), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; the Division of Radiology, Department for Clinical Science (L.B.), Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; the Department of Molecular Medicine (H. Kääriäinen), National Public Health Institute, Helsinki, Finland; the Department of Medical Genetics (M.P.), University of Helsinki, Finland; the Department of Clinical Genetics (M.P.), Helsinki University Central Hospital, Finland; the Department of Pathology (K.M., H. Kalimo), Helsinki University and University Hospital, Finland; the Department of Pathology (H. Kalimo), Uppsala University, Sweden; the Departments of Pathology and Forensic Medicine (H. Kalimo), University of Turku and Turku University Hospital, Finland; and the Department of Geriatric Medicine (M.V.), Turku City Hospital and University of Turku, Finland.

Correspondence to Matti Viitanen, Division of Geriatric Medicine, Karolinska Institutet and Karolinska University Hospital, 14186 Stockholm, Sweden. E-mail matti.viitanen{at}ki.se

Background and Purpose— CADASIL is a hereditary arteriopathy causing recurrent strokes and cognitive decline. Because monozygotic twins have identical genetic background, differences in their environment and lifestyle could reveal factors that may influence CADASIL patients’ clinical course, which is highly variable even within the same family.

Methods— We describe differences in clinical and imaging findings in a pair of monozygotic CADASIL twins.

Results— Twin B experienced his first-ever stroke 14 years earlier than twin A, and his symptoms, signs, and imaging findings were more severe. Distinguishing factors were twin B’s smoking as well as twin A’s physical activity and earlier statin treatment. Causative NOTCH3 mutation was a novel c.752G>A -substitution (p.Cys251Tyr).

Conclusions— The phenotypic differences in these monozygotic twins suggest influence of environmental and lifestyle factors on the clinical course of CADASIL.

Key Words: CADASIL • NOTCH3 monozygotic twins