title: Ocular features in Alport syndrome: pathogenesis and clinical significance.
abstract: Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging.
authors: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia; The University of Melbourne Department of Medicine, Northern Health, Epping, Victoria, Australia; Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia; jasavige@unimelb.edu.au.
authors: Judy
authors: J
authors: Savige
authors: Department of Ophthalmology, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Ophthalmology, Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India;
authors: Shivanand
authors: S
authors: Sheth
authors: Department of Ophthalmology, Universitaire Ziekenhuizen, Leuven, Belgium; and.
authors: Anita
authors: A
authors: Leys
authors: Department of Ophthalmology, Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India;
authors: Anjali
authors: A
authors: Nicholson
authors: Department of Ophthalmology, The University of Melbourne, East Melbourne, Victoria, Australia.
authors: Heather G
authors: HG
authors: Mack
authors: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Ophthalmology, Royal Children's Hospital, Parkville, Victoria, Australia;
authors: Deb
authors: D
authors: Colville
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics; D024141:Collagen Type IV / Q000235:genetics; D003941:Diagnostic Techniques, Ophthalmological; D005128:Eye Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009394:Nephritis, Hereditary / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors
chemical_list: D001324:Autoantigens; C466620:COL4A4 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain
keywords: Alport syndrome; extracellular matrix; genetic renal disease
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