A de novo FBN1 missense variant associated with a severe phenotype of early onset Marfan syndrome

Abstract

Early-onset Marfan syndrome is a rare subtype of Marfan Syndrome (MFS), manifesting early in life. Affected individuals typically present with a severe phenotype, with critical signs and symptoms as early as the neonatal or infantile period, most often due to a de novo pathogenic FBN1 variant. We describe a patient with a rare de novo missense variant c.3284G>C (p.(Cys1095Ser)) in exon 27 in FBN1 leading to early onset MFS with severe cardiovascular involvement including heart enlargement with regurgitation of both atrioventricular valves, aortic dilatation and regurgitation manifest from birth, with a fatal outcome.