Aortic abnormalities in males with Alport syndrome

Clifford E. Kashtan; Yoav Segal; Frances Flinter; David Makanjuola; Jay Sen Gan; Terry Watnick

doi:10.1093/ndt/gfq271

Aortic abnormalities in males with Alport syndrome

Clifford E. Kashtan, Yoav Segal, Frances Flinter, David Makanjuola, Jay Sen Gan, Terry Watnick

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Abstract

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.

Original language	English (US)
Pages (from-to)	3554-3560
Number of pages	7
Journal	Nephrology Dialysis Transplantation
Volume	25
Issue number	11
DOIs	https://doi.org/10.1093/ndt/gfq271
State	Published - Nov 2010

Bibliographical note

Funding Information:
Acknowledgements. The authors thank Drs G. Kirkland and M. Jose for their contributions to the care of Case 5. Dr M. DeBeukelaer provided skin biopsies from members of the Alport family described in ref. 18. The authors also thank Mr Stefan Kren and Ms Julia Mangini for their technical assistance. Y.S. received support from the National Institutes of Health (DK60695) as did T.W. (R01DK70617). C.E.K. is Executive Director of the Alport Syndrome Treatments and Outcomes Registry (http://www.med.umn.edu/peds/astor/home.html). Presentation of patient information was approved by the Institutional Review Board of the University of Minnesota. Portions of this report were presented in abstract form at the Annual Meeting of the American Society of Nephrology in November 2006.

Keywords

Alport syndrome
Aortic aneurysm
Aortic dissection
Type IV collagen

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title = "Aortic abnormalities in males with Alport syndrome",

abstract = "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.",

keywords = "Alport syndrome, Aortic aneurysm, Aortic dissection, Type IV collagen",

author = "Kashtan, {Clifford E.} and Yoav Segal and Frances Flinter and David Makanjuola and Gan, {Jay Sen} and Terry Watnick",

note = "Funding Information: Acknowledgements. The authors thank Drs G. Kirkland and M. Jose for their contributions to the care of Case 5. Dr M. DeBeukelaer provided skin biopsies from members of the Alport family described in ref. 18. The authors also thank Mr Stefan Kren and Ms Julia Mangini for their technical assistance. Y.S. received support from the National Institutes of Health (DK60695) as did T.W. (R01DK70617). C.E.K. is Executive Director of the Alport Syndrome Treatments and Outcomes Registry (http://www.med.umn.edu/peds/astor/home.html). Presentation of patient information was approved by the Institutional Review Board of the University of Minnesota. Portions of this report were presented in abstract form at the Annual Meeting of the American Society of Nephrology in November 2006.",

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AU - Flinter, Frances

AU - Makanjuola, David

AU - Gan, Jay Sen

AU - Watnick, Terry

N1 - Funding Information: Acknowledgements. The authors thank Drs G. Kirkland and M. Jose for their contributions to the care of Case 5. Dr M. DeBeukelaer provided skin biopsies from members of the Alport family described in ref. 18. The authors also thank Mr Stefan Kren and Ms Julia Mangini for their technical assistance. Y.S. received support from the National Institutes of Health (DK60695) as did T.W. (R01DK70617). C.E.K. is Executive Director of the Alport Syndrome Treatments and Outcomes Registry (http://www.med.umn.edu/peds/astor/home.html). Presentation of patient information was approved by the Institutional Review Board of the University of Minnesota. Portions of this report were presented in abstract form at the Annual Meeting of the American Society of Nephrology in November 2006.

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N2 - 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.

AB - 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.

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Aortic abnormalities in males with Alport syndrome

Abstract

Bibliographical note

Keywords

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