Should We Diagnose Autosomal Dominant Alport Syndrome When There Is a Pathogenic Heterozygous COL4A3 or COL4A4 Variant?

Several recent studies have reported a single pathogenic COL4A3 or COL4A4 mutation in up to 30% of individuals undergoing genetic testing for Alport syndrome, and have described this as an autosomal dominant (AD) disease.1–7 However, the use of both AD and Alport syndrome in these circumstances is contentious. Clinicians who use Alport syndrome when there are heterozygous COL4A3 or COL4A4 variants consider that renal failure occurs often enough to justify this diagnosis. In addition, they say that affected individuals must be made aware of their risk of renal failure and the need for ongoing medical supervision.