ALPORT-SYNDROME - A REVIEW OF THE OCULAR MANIFESTATIONS

Alport syndrome has a prevalence of I/5000, and 85% of patients have t he X-linked form, where affected males develop renal failure and usual ly have a high-tone sensorineural deafness by the age of 20. The typic al ocular associations are a dot-and-fleck retinopathy which occurs in about 85% of affected adult males, anterior lenticonus which occurs i n about 25%, and the rare posterior polymorphous corneal dystrophy. Th e retinopathy and anterior lenticonus are not usually demonstrated in childhood but worsen with time so that the retinal lesion is often pre sent at the onset of renal failure, and the anterior lenticonus, later . The demonstration of a dot-and-fleck retinopathy in any individual w ith a family history of Alport syndrome or with end-stage renal diseas e is diagnostic of Alport syndrome. The presence of anterior lenticonu s or posterior polymorphous corneal dystrophy in any individual is hig hly suggestive of the diagnosis of Alport syndrome. Additional ocular features described in X-linked Alport syndrome include other corneal d ystrophies, microcornea, arcus, iris atrophy, cataracts, spontaneous l ens rupture, spherophakia, posterior lenticonus, a poor macular reflex , fluorescein angiogram hyperfluorescence, electrooculogram and electr oretinogram abnormalities, and retinal pigmentation. All mutations dem onstrated to date in X-linked Alport syndrome have affected the COL(4) A(5) gene which encodes the alpha 5 chain of type IV collagen. This pr otein is probably common to the basement membranes of the glomerulus, cochlea, retina, lens capsule, and cornea. However, the alpha 3(IV) an d 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 thes e collagen molecules from the affected basement membranes results in a n abnormal ultrastructural appearance. The ocular and other clinical f eatures 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 me mbrane disease which is a common disease that probably represents the heterozygous expression of X-linked or autosomal recessive Alport synd rome.