Aortic abnormalities in males with Alport syndrome

Background. There have been isolated case reports of arterial disease in males with Alport syndrome (AS), a systemic disorder of Type IV collagen. In this paper, we describe five new cases of AS associated with significant aortic disease including dissection and aneurysm. Methods. We present brief clinical descriptions of five males with AS and aortic disease. We performed immunohistochemical analysis of the expression of the a5 chain of Type IV collagen in skin basement membranes from a previously reported family with AS and associated aortic disease and in the aortic media of male mice with X-linked Alport syndrome (XLAS) due to a nonsense mutation in the COL4A5 gene. Results. Three of the five patients exhibited aneurysm and dissection of the thoracic aorta, occurring at 25-32 years of age, while one had aortic dilatation and another had aortic insufficiency. All five men required renal replacement therapy by age 20. Immunohistochemistry of skin biopsy specimens in previously reported male siblings with aortic disease confirmed that they had XLAS. We further found that the a5 chain of Type IV collagen is abnormally absent from aortic media of transgenic mice with XLAS. Conclusions. Early onset aortic disease may be an unusual feature of AS. Screening of men with AS for aortic abnormalities may be clinically indicated in some families.