Marfan Syndrome

Prevalence is estimated at 1:5000 people.

Inherited as autosomal dominant trait, though 25% of cases are sporadic.

The 2010 Ghent Nosology for Marfan Syndrome guides Dx, heavily prioritizing aortic root dilation, ectopia lentis, and family history.

Aortic rupture and dissection, mitral valve prolapse, mitral or aortic valve regurgitation, arrhythmias, pneumothorax, restrictive lung disease, and chest wall and spine deformity

Ascending aortic dissection and rupture

Mitral and aortic valvular insufficiency

Myocardial ischemia due to medial necrosis of coronary arteries

Dyspnea, reduced functional residual capacity increased risk of pneumothorax

Connective tissue disorder typically inherited via autosomal dominant genetics. Pathophysiology is complex but characterized by a defect of collagen synthesis, which decreases tensile strength and elasticity of connective tissue. CV, particularly aortic, manifestations are most responsible for reduced life expectancy, but the disorder has pansystemic implications.

CV manifestations are most lethal. Pts commonly diagnosed and monitored via transthoracic echocardiography.

Invasive management recommended for type A dissection, type B dissection with severe pain, ischemia, rapid aortic growth, or large aortic diameter. Prophylactic surgery recommended when aortic root exceeds 50 mm or 46 mm in setting of adverse family history, severe valvular involvement, rapid aortic dilation, or planned pregnancy.

Ocular manifestation that is most defining is ectopic lentis, which is the subluxation of the lens

Pts may have a high-arched palate, crowded teeth, abnormal skull shape, malar hypoplasia, or retrognathia. Pts are at risk for spontaneous pneumothorax, restrictive lung disease, and obstructive sleep apnea.

Musculoskeletal features include increased length of long bones, joint laxity, scoliosis, pectus excavatum and carinatum, laxity of cervical spine, and lumbar dural ectasia.

Mutation in FBNI , the gene on chromosome 15 that encodes fibrillin-1, is an extracellular matrix glycoprotein. Fibrillin-1 normally binds TGFβ. Decreased functional fibrillin-1 leads to excess TGFβ, which is thought to lead to a cascade of inflammatory degradation of elastic fibers and extracellular matrix.

The 2010 Revised Ghent Nosology defines diagnostic criteria for Marfan syndrome, including data from aortic imaging, genetic testing, family history, and physical examination.