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Pediatric Nephrology
Published in: Pediatric Nephrology 6/2019

Open Access 01-06-2019 | Maturity-Onset Diabetes of the Young | Original Article

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

Authors: Christine Okorn, Anne Goertz, Udo Vester, Bodo B. Beck, Carsten Bergmann, Sandra Habbig, Jens König, Martin Konrad, Dominik Müller, Jun Oh, Nadina Ortiz-Brüchle, Ludwig Patzer, Raphael Schild, Tomas Seeman, Hagen Staude, Julia Thumfart, Burkhard Tönshoff, Ulrike Walden, Lutz Weber, Marcin Zaniew, Hildegard Zappel, Peter F. Hoyer, Stefanie Weber

Published in: Pediatric Nephrology | Issue 6/2019

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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.
Appendix
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Metadata
Title
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
Authors
Christine Okorn
Anne Goertz
Udo Vester
Bodo B. Beck
Carsten Bergmann
Sandra Habbig
Jens König
Martin Konrad
Dominik Müller
Jun Oh
Nadina Ortiz-Brüchle
Ludwig Patzer
Raphael Schild
Tomas Seeman
Hagen Staude
Julia Thumfart
Burkhard Tönshoff
Ulrike Walden
Lutz Weber
Marcin Zaniew
Hildegard Zappel
Peter F. Hoyer
Stefanie Weber
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-018-4188-8

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