Co-existence of Marfan syndrome and systemic sclerosis: A case report and a hypothesis suggesting a common link

FBN1 gene encodes for the connective tissue protein fibrillin-1 which can also regulate the profibrotic cytokine transforming growth factor (TGF)-ß1. Mutations in the FBN1 gene cause Marfan syndrome (MFS), a genetic condition with defective connective tissues. FBN1 haplotypes and single nucleotide polymorphisms have also been reported to be associated with systemic sclerosis (SSc), a connective tissue disease characterized by fibrosis of multiple organs. Furthermore, the duplication of the Fbn1 gene causes a SSc-like disease in the TsK1 mouse model. To the best of our knowledge, there are no reports of MFS and SSc co-existing in a patient. Here, we describe a 46-year-old woman who presented with cardiac failure. She had a family history of MFS. Physical examination revealed marfanoid habitus and scleroderma features. Echocardiography demonstrated dilated cardiomyopathy with aortic root dilatation, aortic regurgitation and mitral regurgitation. Cardiac magnetic resonance imaging was consistent with dilated cardiomyopathy, mid-wall fibrosis at basal septal wall and dilated aortic root. Extractable nuclear antigen panel detected anti-Scl 70. She fulfilled Ghent criteria for MFS and satisfied American College of Rheumatology/ European League Against Rheumatism classification criteria for SSc. Although we do not have the FBN1 sequence in our patient, the co-existence of MFS and SSc in this patient raises the possibility of co-existence of distinct mutations in the FBN1 gene that could affect TGF-β signaling differently, resulting in divergent pathologic consequences - loss of structural integrity in MFS versus increased extracellular matrix deposition in SSc, and different clinical manifestations.