From clinical mimicry to accurate diagnosis: COL4A4-associated nephropathy hidden behind polycystic kidney disease.

Authors

María Del Mar Del Águila García, Antonio M Poyatos Andújar, Ana I Morales García, María Del Carmen Velázquez de Castro Del Pino, María José Espigares Huete, Rafael J Esteban de la Rosa

Published in

Nefrologia. Pages 501577. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

Type IV collagen related nephropathy caused by heterozygous variants in the COL4A3 or COL4A4 genes shows a wide phenotypic variability, with asymptomatic individuals being relatively common. A cystic phenotype in these cases is uncommon and rarely presents with nephromegaly mimicking autosomal dominant polycystic kidney disease (ADPKD). We report a family with hereditary kidney disease showing an autosomal dominant inheritance pattern and marked phenotypic variability. Some family members were diagnosed with urate nephropathy, others met the Ravine-Pei criteria for ADPKD, and others were labeled as having chronic kidney disease of unknown etiology; five progressed to renal replacement therapy. The proband, who presented with bilateral renal cysts fulfilling ADPKD criteria, along with microhematuria and non-nephrotic proteinuria, tested negative for PKD1 and PKD2 variants after sequential genetic analysis. Meanwhile, another family member studied for persistent microhematuria and non-nephrotic proteinuria underwent a renal biopsy that revealed thinning of the glomerular basement membrane on electron microscopy, suggesting Alport syndrome. Genetic testing in both individuals identified the c.735+2T>C (p?) variant in the COL4A4 gene, classified as likely pathogenic due to its disruption of a splicing site. This case illustrates the phenotypic heterogeneity of heterozygous COL4A4-related Alport syndrome and highlights the importance of implementing genetic testing in the differential diagnosis of hereditary kidney disorders to prevent diagnostic delays with potential clinical consequences.

PMID:
42336693
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.

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