What is Alport syndrome?

Disease Overview

Alport syndrome is an inherited condition that affects the kidneys, hearing, and eyes. It is caused by pathogenic variants (mutations) in the genes that make type IV collagen, a key structural protein in the glomerular basement membrane, the filtering barrier of the kidneys' glomeruli. When this membrane is damaged, the kidneys gradually lose their ability to filter waste and excess fluid from the blood. The same collagen is found in the inner ear and eye, which explains the sensorineural hearing loss and eye abnormalities that often accompany the kidney disease.

Alport syndrome can be inherited in three ways:

• X-linked (COL4A5 gene): historically thought to account for about 80% of diagnoses

• Autosomal recessive (two altered copies of COL4A3 or COL4A4): about 15%

• Autosomal dominant (one altered copy of COL4A3 or COL4A4): traditionally estimated at about 5%, though broader genetic testing suggests it is far more common than once believed

Disease severity depends on the mode of inheritance and sex. Males with X-linked Alport syndrome are usually most severely affected, while females and people with the autosomal dominant form tend to have a milder, more variable course. Early diagnosis and early treatment to protect kidney function can significantly delay disease progression, which is why genetic testing and family screening matter.