Cause:Genetic, autosomal dominant on chromosome 15 (Nejm 1994;331:148; 1992;326:905); however, 15% of cases are sporadic
Pathophys:Defect in elastic collagen caused by fibrillin gene (FBN1) mutation, altering microfibrillar fibers on which elastin is laid (Nejm 2008;358:2829); leads to cystic medial necrosis of thoracic aorta (95%), ocular lens displacement, and other characteristic complc (see below)
Sx:Pos family hx; tall; frequent joint dislocations with minor trauma
Si:Arachnodactyly, arm span > height; hernias; lenticular dislocations (80%), upward, unlike downward in homocystinuria; aortic insufficiency (60%) with click, also mitral insufficiency due to posterior leaflet prolapse; arched palate
Average age at death is 32 yr, most from aortic root dilatation causes such as dissection, rupture, and aortic and mitral insufficiencies (Nejm 1972;286:804)
Aortic dissection (12%), accounts for 90% of deaths so caution with clearance for sports (Nejm 1986;314:1070); SBE; vascular rupture during pregnancy (Ann IM 1995;123:117)
r/o homocystinuria (Homocystinuria (Homocyst[e]inemia)); EHLERS-DANLOS syndrome (Nejm 2001;345:1167; 2000;342:675, 730) due to genetic collagen defects; all types have skin fragility, bruising, DJD; type IVs die from aortic, arterial, bowel, or uterine rupture; not usually assoc w hyperextensibility types
Rx: Perhaps ARB rx (Nejm 2008;358:2787, 2829)
of scoliosis (Scoliosis)
of ascending aortic aneurysm: propranolol qid po or other 
-blocker to keep exercise P <100, slows progression of aortic disease (Science 2006;312:117; Nejm 1994;330:1335); or surgical when 6+ cm