Clinical Spectrum and Early Renal Functional Variability in a Nationwide Greek Pediatric HNF1B Multicenter Cohort.

Background/Objectives: Hepatocyte nuclear factor 1 beta (HNF1B)-associated disease is a major monogenic cause of pediatric cystic kidney disease. This study characterized the clinical, genetic, renal, and extrarenal spectrum of HNF1B-associated disease in a nationwide Greek pediatric cohort, with emphasis on renal functional variability during childhood. Methods: In this retrospective multicenter cohort study, 20 children aged <18 years with molecularly characterized HNF1B-associated disease were identified from eight pediatric nephrology centers across Greece. Clinical, genetic, laboratory, imaging, and kidney function data were analyzed. Estimated glomerular filtration rate (eGFR) was assessed at diagnosis and latest follow-up, and genotype-phenotype comparisons were performed. Results: Median age at diagnosis was 5.0 years. Copy-number variants were identified in 12 patients (60.0%), including ten 17q12 microdeletions and two whole-gene HNF1B deletions, while eight patients (40.0%) carried intragenic variants. Renal cysts were present in 95.0% of patients, hyperechogenic kidneys in 70.0%, and congenital anomalies of the kidney and urinary tract (CAKUT) in 20.0%. Hypomagnesemia was observed in 25.0% of patients, while hyperuricemia was identified in 29.4% of those with available measurements. Longitudinal eGFR data were available for 19 patients. Over a median follow-up of 5.0 years, mean eGFR remained largely unchanged (84.5 ± 19.8 vs. 84.0 ± 16.7 mL/min/1.73 m2); however, substantial interindividual variability was observed. No statistically significant genotype-phenotype associations were identified, although hypomagnesemia was more frequent among patients with deletion-type defects. Conclusions: This nationwide Greek pediatric cohort highlights the marked phenotypic heterogeneity of HNF1B-associated disease, characterized by predominant structural renal abnormalities and relatively stable kidney function during childhood. Larger studies are needed to better define genotype-specific outcomes.