A TRIM8 Variant in a Child: Neuro-Renal Syndrome Causing Features Suggestive of Medullary Sponge Kidney

Medullary sponge kidney (MSK) is a rare congenital renal anomaly characterised by cystic dilatation of the collecting ducts, often asymptomatic but occasionally presenting with hematuria, nephrolithiasis, or urinary tract infections. While familial cases exist, its precise genetic basis remains unclear. The TRIM8 gene encodes an E3 ubiquitin ligase involved in regulating cellular proliferation, immune response, and differentiation. Pathogenic TRIM8 variants have predominantly been linked to neurodevelopmental disorders and steroid-resistant nephrotic syndrome (SRNS), with or without neurological involvement. Here, we report the case of an 11-year-old boy with incidental proteinuria, later diagnosed with MSK based on ultrasonography showing increased medullary echogenicity. He exhibited persistent nephrotic-range proteinuria despite corticosteroid therapy, accompanied by neurodevelopmental delay. Genetic analysis revealed a heterozygous likely pathogenic c.1193dup (p.Gln399Profs11) variant in TRIM8, supporting a diagnosis of neuro-renal syndrome. This is the first reported case to suggest a possible association between a TRIM8 mutation and the development of MSK. The patient's case expands the known renal phenotype associated with TRIM8-related disorders, highlighting that TRIM8 dysfunction may contribute to tubular abnormalities leading to a spongy medullary phenotype. Further studies are needed to investigate the role of TRIM8 and related signalling pathways in congenital tubular anomalies and their place in the genetic aetiology of MSK.