Marfan Syndrome

Excerpt

One of the most common inherited disorders affecting connective tissue, Marfan syndrome (MFS), is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals. The defect is in the FBN1 gene of chromosome 15, which produces fibrillin, a connective tissue protein. There is a broad range of clinical severity associated with MFS, ranging from isolated features of MFS to neonatal presentation of severe and rapidly progressive disease involving multiple organ systems. The syndrome is associated with classic ocular, cardiovascular, and musculoskeletal abnormalities, although involvement of the lung, skin, and central nervous system may also occur. Decreased life expectancy occurs primarily due to aortic complications, including aortic root dilatation and dissection.

The patients with MFS display multiple deformities of the skeleton, including dolichostenomelia (long limbs compared to trunk), arachnodactyly (abnormally long and thin digits), thoracolumbar scoliosis, and pectus deformities (excavatum and carinatum). Aortic regurgitation, dilatation, and aneurysms are most common in the cardiovascular system. Mitral valve prolapse can also occur. Ocular findings include lens dislocation, cataracts, myopia, and retinal detachment. The diagnosis of MFS is usually made clinically based on typical abnormalities. Craniofacial characteristics, thumb and wrist signs, severe hindfoot valgus, and pectus carinatum are the physical features with the highest diagnostic yield. There is no specific laboratory test except molecular genetic testing for diagnosing MFS. No specific treatment cures MFS, but specific interventions may improve certain aspects of the syndrome. Medical therapy with beta-blockers and other afterload-reducing agents aims to reduce stress on the aortic valve, mitral valve, and aortic root. Outcome improves with early diagnosis, medical treatment to delay or prevent the progression of aortic dilatation, and timely elective surgery.