Published Online
on April 16, 2009

A more recent version of this article appeared on June 1, 2009

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Submitted on August 12, 2008
Revised on October 15, 2008
Accepted on November 4, 2008

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; and 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.

^* To whom correspondence should be addressed. 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