BACKGROUND: HNF1B gene mutations are an important cause of bilateral (cystic) dysplasia in children, complicated by chronic renal insufficiency. The clinical variability, the absence of genotype-phenotype correlations, and limited long-term data render counseling of affected families difficult. METHODS: Longitudinal data of 62 children probands with genetically proven HNF1B nephropathy was obtained in a multicenter approach. Genetic family cascade screening was performed in 30/62 cases. RESULTS: Eighty-seven percent of patients had bilateral dysplasia, 74% visible bilateral, and 16% unilateral renal cysts at the end of observation. Cyst development was non-progressive in 72% with a mean glomerular filtration rate (GFR) loss of - 0.33 ml/min/1.73m2 per year (± 8.9). In patients with an increase in cyst number, the annual GFR reduction was - 2.8 ml/min/1.73m2 (± 13.2), in the total cohort - 1.0 ml/min/1.73m2 (±10.3). A subset of HNF1B patients differs from this group and develops end stage renal disease (ESRD) at very early ages < 2 years. Hyperuricemia (37%) was a frequent finding at young age (median 1 year), whereas hypomagnesemia (24%), elevated liver enzymes (21%), and hyperglycemia (8%) showed an increased incidence in the teenaged child. Genetic analysis revealed no genotype-phenotype correlations but a significant parent-of-origin effect with a preponderance of 81% of maternal inheritance in dominant cases. CONCLUSIONS: In most children, HNF1B nephropathy has a non-progressive course of cyst development and a slow-progressive course of kidney function. A subgroup of patients developed ESRD at very young age < 2 years requiring special medical attention. The parent-of-origin effect suggests an influence of epigenetic modifiers in HNF1B disease.

Bergmann Laboratory University Medical Center Freiburg Freiburg Germany

Children's Hospital Augsburg Augsburg Germany

Children's Hospital St Elisabeth and St Barbara Halle Germany

Cologne Center for Genomics University of Cologne Cologne Germany

Department of Pediatrics University of Zielona Góra Zielona Góra Poland

Institute of Human Genetics RWTH University Hospital Aachen Aachen Germany

Institute of Human Genetics University Hospital of Cologne Cologne Germany

Pediatric Nephrology Pediatrics 2 University of Duisburg Essen Essen Germany

Pediatric Nephrology University Campus Virchow University Children's Hospital Berlin Berlin Germany

Pediatric Nephrology University Children's Hospital Cologne Cologne Germany

Pediatric Nephrology University Children's Hospital Hamburg Hamburg Germany

Pediatric Nephrology University Children's Hospital Heidelberg Heidelberg Germany

Pediatric Nephrology University Children's Hospital Marburg Baldingerstrasse 1 35033 Marburg Germany

Pediatric Nephrology University Children's Hospital Münster Münster Germany

Pediatric Nephrology University Children's Hospital Prague Prague Czech Republic

Pediatric Nephrology University Children's Hospital Rostock Rostock Germany

University Children's Hospital Göttingen Göttingen Germany

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