Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease and Alport Syndrome: Two Familial Cases Illustrating Diagnostic Challenges

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder and leads to the formation of kidney cysts, kidney enlargement, and kidney failure. We present a male patient initially misdiagnosed with ADPKD, partly based on his family history, who was later diagnosed with digenic Alport syndrome caused by pathogenic variants in COL4A4 and COL4A5. Digenic Alport syndrome was subsequently diagnosed in 3 of his sisters, one of whom had previously been diagnosed with ADPKD, due to a de novo heterozygous pathogenic variant in PKD1. She had experienced an unusual clinical course for a patient with ADPKD, with remarkably rapid kidney function decline, persistent microscopic hematuria, and overt proteinuria. Through these cases, we aim to highlight alternative genetic causes of kidney cysts beyond ADPKD, describe how the phenotypical features in these cases were not fully explained by their known genotypes (leading to alternative or additional genetic diagnoses), and illustrate the importance of accurate genetic diagnoses for cascade screening.