Aortic Abnormalities in Males with Alport Syndrome

Overview

Journal Nephrol Dial Transplant

Publisher Oxford University Press

Specialties General Surgery
Nephrology

Date 2010 May 25

PMID 20494893

Citations 24

Authors

Clifford E Kashtan

Yoav Segal

Frances Flinter

David Makanjuola

Jay-Sen Gan

Terry Watnick

Affiliations

Soon will be listed here.

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 α5 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 α5 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.

Citing Articles

Aberrant right renal perfusion from right internal mammary artery.

Patel A, Park W, Chenbhanich J, Gornik H, Cho J J Vasc Surg Cases Innov Tech. 2025; 11(2):101713.

PMID: 39886218 PMC: 11780940. DOI: 10.1016/j.jvscit.2024.101713.

Identification of Variants of Uncertain Significance in the Genes Associated with Thoracic Aortic Disease in Russian Patients with Nonsyndromic Sporadic Subtypes of the Disorder.

Goncharova I, Shipulina S, Sleptcov A, Zarubin A, Valiakhmetov N, Panfilov D Int J Mol Sci. 2024; 25(15).

PMID: 39125885 PMC: 11312146. DOI: 10.3390/ijms25158315.

Ascending aortic aneurysm and histopathology in Alport syndrome: a case report.

Kamiar A, Alitter Q, Capcha J, Saad A, Webster K, Shehadeh L BMC Nephrol. 2023; 24(1):300.

PMID: 37828432 PMC: 10568822. DOI: 10.1186/s12882-023-03345-5.

Vertebral and Basilar Artery Dissection in a Patient With Alport Syndrome.

Talbot-Stetsko H, Saleh S, Brent A, Camelo-Piragua S, Gordon D, Williamson C Neurohospitalist. 2023; 13(4):410-414.

PMID: 37701259 PMC: 10494822. DOI: 10.1177/19418744231175561.

Alport Syndrome and Oral Mucous Membrane Pemphigoid: An Interesting Case.

Zisis V, Dimitrios A, Kasimatis E, Vakirlis E, Poulopoulos A Cureus. 2023; 15(7):e41519.

PMID: 37551211 PMC: 10404443. DOI: 10.7759/cureus.41519.

References

Golledge J, Muller J, Daugherty A, Norman P . Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol. 2006; 26(12):2605-13. DOI: 10.1161/01.ATV.0000245819.32762.cb. View

Wolinsky H, Glagov S . A lamellar unit of aortic medial structure and function in mammals. Circ Res. 1967; 20(1):99-111. DOI: 10.1161/01.res.20.1.99. View

Ding J, Zhou J, Tryggvason K, Kashtan C . COL4A5 deletions in three patients with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. J Am Soc Nephrol. 1994; 5(2):161-8. DOI: 10.1681/ASN.V52161. View

Zehnder A, Adams J, Santi P, Kristiansen A, Wacharasindhu C, Mann S . Distribution of type IV collagen in the cochlea in Alport syndrome. Arch Otolaryngol Head Neck Surg. 2005; 131(11):1007-13. DOI: 10.1001/archotol.131.11.1007. View

Sariola H, Viljanen T, Luosto R . Histological pattern and changes in extracellular matrix in aortic dissections. J Clin Pathol. 1986; 39(10):1074-81. PMC: 500225. DOI: 10.1136/jcp.39.10.1074. View

Cheong H, Kashtan C, Kim Y, Kleppel M, Michael A . Immunohistologic studies of type IV collagen in anterior lens capsules of patients with Alport syndrome. Lab Invest. 1994; 70(4):553-7. View

Peissel B, Geng L, Kalluri R, Kashtan C, Rennke H, Gallo G . Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients. J Clin Invest. 1995; 96(4):1948-57. PMC: 185832. DOI: 10.1172/JCI118241. View

Judge D, Dietz H . Marfan's syndrome. Lancet. 2005; 366(9501):1965-76. PMC: 1513064. DOI: 10.1016/S0140-6736(05)67789-6. View

van der Loop F, Monnens L, Schroder C, Lemmink H, Breuning M, Timmer E . Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin. Kidney Int. 1999; 55(4):1217-24. DOI: 10.1046/j.1523-1755.1999.00357.x. View

10.

Vogt B, Birk P, Panzarino V, Hite S, Kashtan C . Aortic dissection in young patients with chronic hypertension. Am J Kidney Dis. 1999; 33(2):374-8. DOI: 10.1016/s0272-6386(99)70315-x. View

11.

Seki T, Naito I, Oohashi T, Sado Y, Ninomiya Y . Differential expression of type IV collagen isoforms, alpha5(IV) and alpha6(IV) chains, in basement membranes surrounding smooth muscle cells. Histochem Cell Biol. 1998; 110(4):359-66. DOI: 10.1007/s004180050296. View

12.

Gould D, Phalan F, van Mil S, Sundberg J, Vahedi K, Massin P . Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006; 354(14):1489-96. DOI: 10.1056/NEJMoa053727. View

13.

Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont M . COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med. 2007; 357(26):2687-95. DOI: 10.1056/NEJMoa071906. View

14.

Gould D, Phalan F, Breedveld G, van Mil S, Smith R, Schimenti J . Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005; 308(5725):1167-71. DOI: 10.1126/science.1109418. View

15.

Lyons O, St John E, Morales J, Chan Y, Taylor P . Ruptured thoracoabdominal aortic aneurysm in a renal transplant patient with Alport's syndrome. Ann Vasc Surg. 2007; 21(6):816-8. DOI: 10.1016/j.avsg.2007.06.004. View

16.

Pannu H, Avidan N, Tran-Fadulu V, Milewicz D . Genetic basis of thoracic aortic aneurysms and dissections: potential relevance to abdominal aortic aneurysms. Ann N Y Acad Sci. 2006; 1085:242-55. DOI: 10.1196/annals.1383.024. View

17.

Hudson B . The molecular basis of Goodpasture and Alport syndromes: beacons for the discovery of the collagen IV family. J Am Soc Nephrol. 2004; 15(10):2514-27. DOI: 10.1097/01.ASN.0000141462.00630.76. View

18.

van der Knaap M, Smit L, Barkhof F, Pijnenburg Y, Zweegman S, Niessen H . Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. Ann Neurol. 2005; 59(3):504-11. DOI: 10.1002/ana.20715. View

19.

Dingemans K, Teeling P, Lagendijk J, Becker A . Extracellular matrix of the human aortic media: an ultrastructural histochemical and immunohistochemical study of the adult aortic media. Anat Rec. 1999; 258(1):1-14. DOI: 10.1002/(SICI)1097-0185(20000101)258:1<1::AID-AR1>3.0.CO;2-7. View

20.

Kashtan C, Butkowski R, Kleppel M, First M, Michael A . Posttransplant anti-glomerular basement membrane nephritis in related males with Alport syndrome. J Lab Clin Med. 1990; 116(4):508-15. View