Transient Nephrotic Syndrome in an Infant With Heterozygous Variants of Uncertain Significance in LMX1B and TTC21B

Infantile nephrotic syndrome is rare and frequently associated with an underlying genetic cause. Oligogenic inheritance has been proposed in selected cases, although supporting evidence remains limited. We report the case of an 8-month-old infant presenting with nephrotic syndrome characterized by massive proteinuria (25 g/g creatinine), hypoalbuminemia (17 g/L), and preserved renal function. Genetic testing using a targeted nephrotic syndrome panel identified two heterozygous variants of uncertain significance (American College of Medical Genetics and Genomics (ACMG) class 3) in LMX1B and TTC21B. The patient's mother carried both variants, whereas the maternal grandfather carried only the LMX1B variant. No corticosteroids or immunosuppressive therapy were administered. Supportive treatment alone resulted in complete remission by 12 months of age, which has been maintained through the latest follow-up at 3 years and 8 months. The coexistence of two variants of uncertain significance raises the possibility of a genetic contribution to the phenotype; however, the available evidence is insufficient to establish a causal oligogenic mechanism. This case highlights the unusual occurrence of sustained spontaneous remission in infantile nephrotic syndrome and illustrates the challenges of interpreting variants of uncertain significance in clinical practice.