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

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.