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

Abstract: 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: issn: 1432-198X

Classification and Topics

• Keyword: Zystenniere ; Magnesiummangel

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Okorn, Christine ; Goertz, Anne ; Vester, Udo ; Beck, Bodo Bernhard ; Bergmann, Carsten ; Habbig, Sandra ; König, Jens ; Konrad, Martin ; Müller, Dominik ; Oh, Jun ; Ortiz Brüchle, Nadina Carola ; Patzer, Ludwig ; Schild, Raphael-Sebastian ; Seeman, Tomáš ; Staude, Hagen ; Thumfart, Julia Angelika ; Tönshoff, Burkhard ; Walden, Ulrike ; Weber, Lutz T. ; Zaniew, Marcin ; Zappel, Hildegard ; Hoyer, Peter F. ; Weber, Stefanie

Further information

• DOI: 10.1007/s00467-018-4188-8
• URN: urn:nbn:de:bsz:25-freidok-1498894
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:32 AM CEST