HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: results of the German Multicenter HNF1B Childhood Registry

Pediatr Nephrol. 2019 Jun;34(6):1065-1075. doi: 10.1007/s00467-018-4188-8. Epub 2019 Jan 21.


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.

Keywords: Cystic kidney disease; GFR decline; HNF1B; Hypomagnesemia; MODY.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Genetic Association Studies
  • Germany
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney Failure, Chronic / genetics
  • Male
  • Phenotype
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / pathology*
  • Polycystic Kidney Diseases / physiopathology*
  • Registries


  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta