Marfan syndrome: an update of genetics, medical and surgical management

arfan syndrome is a heritable disorder of the connective tissue with an estimated prevalence of 1 in 5000 individuals and no predilection for either sex. The syndrome is inherited as an autosomal dominant trait with complete penetrance but with phenotypic expression that varies considerably, both between and within families. Severe forms such as neonatal Marfan syndrome with ,1 year survival usually result from de novo mutations, whereas about 75% of persons with classic Marfan syndrome have a positive family history. Affected individuals develop varying patterns of organ involvement including the cardiovascular, ocular, skeletal, and pulmonary system, the skin, and the dura. In classical Marfan syndrome, many manifestations present during puberty or later and severe complications rarely develop before adulthood. Such complications include severe scoliosis or pectus excavatum, spontaneous pneumothorax, retinal detachment or sight-threatening glaucoma resulting from dislocated lenses. Before the evolution of open heart surgery, however, Marfan patients usually died from acute aortic dissection or rupture, and thus had an average life-expectancy of only 32 years. The principles for managing cardiovascular manifestations have remained remarkably unchanged over the past 25 years and Marfan patients have been shown to adhere excellently to medication and physical activity guidelines. However, the classical standards have currently been challenged by two major developments. First, with the increasing life expectancy of Marfan patients there is a shift in the spectrum of medical problems. Second, recent molecular, surgical and clinical research has yielded profound new insights into the pathogenesis and treatment options of inherited connective tissue disorders. This article contrasts classical concepts with recent advances to highlight their potential impact on future concepts of patient care. 2