Abstract
<jats:p> Alport syndrome (AS) is a hereditary nephropathy caused by mutations in the <jats:italic>COL4A3</jats:italic> , <jats:italic>COL4A4</jats:italic> , and <jats:italic>COL4A5</jats:italic> genes. Rare contiguous <jats:italic>COL4A5–COL4A6</jats:italic> alterations cause AS with diffuse leiomyomatosis (AS-DL). </jats:p> <jats:p> <jats:bold>Case report.</jats:bold> A 16-year-old male had mild proteinuria, hematuria, hearing loss and myopia since childhood. Estimated glomerular filtration rate was 82.8 mL/min/1.73 m <jats:sup>2</jats:sup> . Kidney biopsy showed segmental mesangial sclerosis; immunofluorescence was negative. Electron microscopy demonstrated diffuse glomerular basement membrane thinning and podocyte foot-process effacement. Two deceased brothers had end stage kidney disease; the mother had hematuria, uterine myoma, and a benign bladder tumor. A diagnosis of X-linked AS was established according to the Flinter criteria and nephroprotective treatment was initiated. Since 2024, the patient had complained of epigastric symptoms. An endoscopy revealed a 2-cm gastric submucosal lesion. A whole-exome sequencing identified a hemizygous missense variant in <jats:italic>COL4A5</jats:italic> and a <jats:italic>COL4A6</jats:italic> exon 1–2 deletion, confirming AS-DL. </jats:p> <jats:p> <jats:bold>Discussion.</jats:bold> This case demonstrates the co-occurrence of AS-DL and shows that early pedigree assessment, combined with integrated clinicopathologic-genetic evaluation in a multidisciplinary framework, enables a timely diagnosis of atypical familial AS-DL and improves clinical management. </jats:p>