XL Alport syndrome results from a single pathogenic variant in the COL4A5 gene which encodes the collagen IV alpha 5 chain. This chain results in a heterotrimer with the collagen IV alpha 3 and alpha 4 chains, that forms the main network of the basement membranes in the kidney, ear and eye. All these tissues may be affected in Alport syndrome.
XL Alport syndrome affects at least one in 2000 people, but while the characteristic features are present in all affected males, there are twice as many affected females with typically milder disease. Males with XL Alport syndrome have haematuria, progressive kidney failure, hearing loss and ocular abnormalities (lenticonus, fleck retinopathy). Kidney failure is present in 90% of men by the age of 40. None of an affected male’s sons are affected but all of his daughters are. For each affected male there are two women (his mother, sisters or daughters) who should be identified and treated.
About 20% of affected females have kidney failure by the age of 60 although hearing loss and a fleck retinopathy are common in middle age. Half of an affected female’s sons and half her daughters are affected.
COL4A5