Genetic causes and therapy in Alport Syndrome

Patients with the hereditary disease Alport syndrome (AS) develop progressive renal fibrosis due to variants in type IV collagen genes. In the first years of life, AS starts with hematuria and proteinuria, finally leading to end-stage renal disease and extrarenal symptoms such as hearing impairment and ocular changes. Variants in three different genes can cause AS, COL4A5 (X-chromosomal) in 85%, COL4A3 or COL4A4 (autosomal) in 10%, and digenic variants in less than 5% of the cases. In the past, the symptomatic form in patients with a heterozygous variant was classified as thin basementmembrane disease or benign familial hematuria. However, patients with a heterozygous variant often have a non-benign disease course. Therefore, these patients are now also given the diagnosis "Alport syndrome." If diagnosed early, AS is treatable. Renal failure can be delayed by years and life expectancy can be improved. Because of the available treatment options, the molecular genetic diagnosis should bemade as soon as possible in every affected child and in all patients with a heterozygous variant. Unfortunately, the diagnosis is often made too late during early adolescence. This article serves as a guideline for the genetic background of AS, possible additional (genetic) modifiers, possible additional complications, and the current therapeutic approach for the optimal lifelong care of patients living with AS. For genetic experts, it is important to know that this nephroprotective approach begins with an early genetic diagnosis guiding the timeline of possible therapeutic interventions.     «

Patients with the hereditary disease Alport syndrome (AS) develop progressive renal fibrosis due to variants in type IV collagen genes. In the first years of life, AS starts with hematuria and proteinuria, finally leading to end-stage renal disease and extrarenal symptoms such as hearing impairment and ocular changes. Variants in three different genes can cause AS, COL4A5 (X-chromosomal) in 85%, COL4A3 or COL4A4 (autosomal) in 10%, and digenic variants in less than 5% of the cases. In the past,...     »