Alport syndrome. A review of the ocular manifestations

Ophthalmic Genet. 1997 Dec;18(4):161-73. doi: 10.3109/13816819709041431.

Abstract

Alport syndrome has a prevalence of 1/5000, and 85% of patients have the X-linked form, where affected males develop renal failure and usually have a high-tone sensorineural deafness by the age of 20. The typical ocular associations are a dot-and-fleck retinopathy which occurs in about 85% of affected adult males, anterior lenticonus which occurs in about 25%, and the rare posterior polymorphous corneal dystrophy. The retinopathy and anterior lenticonus are not usually demonstrated in childhood but worsen with time so that the retinal lesion is often present at the onset of renal failure, and the anterior lenticonus, later. The demonstration of a dot-and-fleck retinopathy in any individual with a family history of Alport syndrome or with end-stage renal disease is diagnostic of Alport syndrome. The presence of anterior lenticonus or posterior polymorphous corneal dystrophy in any individual is highly suggestive of the diagnosis of Alport syndrome. Additional ocular features described in X-linked Alport syndrome include other corneal dystrophies, microcornea, arcus, iris atrophy, cataracts, spontaneous lens rupture, spherophakia, posterior lenticonus, a poor macular reflex, fluorescein angiogram hyperfluorescence, electrooculogram and electroretinogram abnormalities, and retinal pigmentation. All mutations demonstrated to date in X-linked Alport syndrome have affected the COL4A5 gene which encodes the alpha 5 chain of type IV collagen. This protein is probably common to the basement membranes of the glomerulus, cochlea, retina, lens capsule, and cornea. However, the alpha 3(IV) and 4(IV) as well as the alpha 5(IV) collagen chains are usually absent from the affected basement membranes, because the abnormal alpha 5(IV) molecule interferes with the stability of all three. The loss of these collagen molecules from the affected basement membranes results in an abnormal ultrastructural appearance. The ocular and other clinical features of autosomal recessive Alport syndrome are identical to those seen in X-linked disease, while retinopathy and cataracts are the only ocular abnormalities described in the rare autosomal dominant form of Alport syndrome. There are no ocular associations of thin basement membrane disease which is a common disease that probably represents the heterozygous expression of X-linked or autosomal recessive Alport syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basement Membrane / pathology
  • Basement Membrane / ultrastructure
  • Cataract
  • Collagen / genetics
  • Corneal Dystrophies, Hereditary / etiology*
  • Corneal Dystrophies, Hereditary / genetics
  • Corneal Dystrophies, Hereditary / pathology
  • Disease Models, Animal
  • Fundus Oculi
  • Genetic Linkage
  • Humans
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure
  • Lens Diseases / etiology*
  • Lens Diseases / genetics
  • Lens Diseases / pathology
  • Male
  • Nephritis, Hereditary / complications*
  • Nephritis, Hereditary / genetics
  • Nephritis, Hereditary / pathology
  • Retinal Diseases / etiology*
  • Retinal Diseases / genetics
  • Retinal Diseases / pathology
  • X Chromosome

Substances

  • Collagen