Marfan syndrome and sudden death within a family - Aetiologic, molecular and diagnostic issues at autopsy

Abstract

Although Marfan syndrome has a range of characteristic morphological features involving the ocular, cardiovascular and musculoskeletal systems, the phenotype is variable. In addition, mutations have been identified in the gene encoding for fibrillin-1 and also in the transforming growth factor-beta receptor 2 (TGF-betaR2) gene. Two cases are presented of sudden and unexpected deaths in cousins who manifested morphologic features of Marfan syndrome at autopsy. Case 1: A 36-year-old male who collapsed and was found at autopsy to have arachnodactyly, a high arched palate and lethal aortic dissection with haemopericardium. Case 2: A 34-year-old male who collapsed and was found at autopsy to have arachnodactyly, a high arched palate, pes cavus and a dysplastic mitral valve. Current aetiological theories and molecular findings are discussed. While family follow-up and counselling are advised when cases come to autopsy, given the variability in phenotype and genotype, and the difficulties that exist in attempting to determine clinical prognosis from either of these, such deaths may raise more concerns for surviving family members than providing answers.