[Marfan syndrome presenting with cervical tortuous arteries and subcortical hemorrhage: a case with a mutation in an intron of the FBN1 gene].

A 39-year-old man was admitted to our hospital because of left frontal subcortical hemorrhage.When he was 22, he underwent an operation for aortic dilatation and aortic valve regurgitation, and he had been taking warfarin since then. At that hospital, he was diagnosed with Marfan syndrome (MFS) on the basis of his clinical features, but the diagnosis was not confirmed genetically. Head radiological imaging did not reveal the abnormal blood vessels causing subcortical hemorrhage, but T2* magnetic resonance imaging showed many micro-bleeds in the subcortical areas and basal ganglia. Moreover, cerebral angiography showed marked tortuous carotid and vertebral both arteries in his neck; these findings suggested the possibility of Loeys-Dietz syndrome. Genetic analysis revealed a single-base substitution (c.3713-3C>G) at the -3 position in the 29th intron of the FBN1 gene, encoding the fibrillin-1 protein. This mutation was not observed in his parents but was detected in his two sons who manifested the physical features of MFS. Therefore, this mutation was considered to be a de novo mutation exhibiting a new pathogenic mechanism involving abnormal splicing. The presented case is unique in that the patient with MFS showed subcortical hemorrhage and had a novel de novo mutation in the FBN1 gene.