Management of Marfan syndrome.

Marfan syndrome is a variable, autosomal dominant connective tissue disorder, affecting mainly the cardiovascular system, eyes, and skeleton. The incidence is approximately 1 in 9800, and around 26% of cases have no family history, the condition resulting from a new mutation. Characteristic features include progressive aortic dilatation associated with aortic valve incompetence, mitral valve prolapse and incompetence, lens dislocation and myopia, and a tall and thin body (fig 1) with long limbs, arachnodactyly, pectus deformities, and sometimes scoliosis. Further less specific features are often detectable in the clinic, such as a high palate with dental crowding, and skin striae distensae, and other characteristic findings may be sought by radiological imaging, such as protrusio acetabulae and dural ectasia. A history of recurrent pneumothorax may be found in some cases. The clinical features have been codified into the so-called Ghent diagnostic nosology, as the clinical variability of the condition can otherwise make diagnosis difficult. Life expectancy is primarily determined by the severity of cardiovascular involvement, and has improved substantially in the past 30 years as a result of improved medical and surgical management. In particular, β blockade reduces the rate of aortic dilatation in some patients, and, perhaps not surprisingly, the outcome of prophylactic aortic root surgery has been shown in several recent series to be superior to that of emergency surgery for dissecting aneurysm. The timing of prophylactic surgical intervention depends on a number of factors including the aortic diameter and its rate of dilatation, implying a need for regular aortic root surveillance. The optimal management of Marfan patients may therefore require lifelong medical treatment, and lifelong aortic surveillance with a view to potential aortic root surgery, representing a major commitment for patient and doctor alike. At the same time, a diagnosis of Marfan syndrome may have serious social consequences for the patient, in terms of lifestyle, employment, and insurance. Marfan syndrome almost always results from mutation in the fibrillin 1 gene on chromosome 15, although in one family the disease was linked to an unknown gene on chromosome 3. Molecular testing for Marfan syndrome has proved less useful than was hoped for two main reasons. Firstly, very few fibrillin 1 mutations have been observed more than once, so the detection of a mutation yields little prognostic information beyond that available from the patient’s own family history. Secondly, fibrillin 1 mutations have also been detected in Marfan related disorders whose cardiovascular involvement is milder or non-existent. These include MASS syndrome, a disorder with some Marfan-like features (myopia, mitral valve prolapse, aortic dilatation, skin involvement, skeletal involvement) but mild and apparently stable aortic dilatation, and isolated ectopia lentis. The importance of a careful clinical assessment and accurate clinical diagnosis cannot therefore be overstated, if appropriate targeting of medical and surgical resources in Marfan patients is to be achieved. In this article, I will review current approaches to diagnosis of Marfan syndrome and cardiovascular management.