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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

Okorn, Christine
Author Okorn, Christine Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany
Goertz, Anne
Author Goertz, Anne Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany
Vester, Udo
Author Vester, Udo Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany
Beck, Bodo B
Author Beck, Bodo B Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany Cologne Center for Genomics (CCG) and Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Bergmann, Carsten
Author Bergmann, Carsten Bergmann Laboratory, University Medical Center Freiburg, Freiburg, Germany
Habbig, Sandra
Author Habbig, Sandra Pediatric Nephrology, University Children's Hospital Cologne, Cologne, Germany
König, Jens
Author König, Jens Pediatric Nephrology, University Children's Hospital Münster, Münster, Germany
Konrad, Martin
Author Konrad, Martin Pediatric Nephrology, University Children's Hospital Münster, Münster, Germany
Müller, Dominik
Author Müller, Dominik Pediatric Nephrology, University Campus Virchow University Children's Hospital Berlin, Berlin, Germany
Oh, Jun
Author Oh, Jun Pediatric Nephrology, University Children's Hospital Hamburg, Hamburg, Germany
Ortiz-Brüchle, Nadina
Author Ortiz-Brüchle, Nadina Institute of Human Genetics, RWTH University Hospital Aachen, Aachen, Germany
Patzer, Ludwig
Author Patzer, Ludwig Children's Hospital St. Elisabeth and St. Barbara, Halle (Saale), Germany
Schild, Raphael
Author Schild, Raphael Pediatric Nephrology, University Children's Hospital Hamburg, Hamburg, Germany
Seeman, Tomas
Author Seeman, Tomas Pediatric Nephrology, University Children's Hospital Prague, Prague, Czech Republic
Staude, Hagen
Author Staude, Hagen Pediatric Nephrology, University Children's Hospital Rostock, Rostock, Germany
Thumfart, Julia
Author Thumfart, Julia Pediatric Nephrology, University Campus Virchow University Children's Hospital Berlin, Berlin, Germany
Tönshoff, Burkhard
Author Tönshoff, Burkhard Pediatric Nephrology, University Children's Hospital Heidelberg, Heidelberg, Germany
Walden, Ulrike
Author Walden, Ulrike Children's Hospital Augsburg, Augsburg, Germany
Weber, Lutz
Author Weber, Lutz Pediatric Nephrology, University Children's Hospital Cologne, Cologne, Germany
Zaniew, Marcin
Author Zaniew, Marcin Department of Pediatrics, University of Zielona Góra, Zielona Góra, Poland
Zappel, Hildegard
Author Zappel, Hildegard University Children's Hospital Göttingen, Göttingen, Germany
Hoyer, Peter F
Author Hoyer, Peter F Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany
Weber, Stefanie
Author Weber, Stefanie Pediatric Nephrology, University Children's Hospital Marburg, Baldingerstrasse 1, 35033, Marburg, Germany. Stefanie.weber@med.uni-marburg.de

Pediatric nephrology (Berlin, Germany). 2019 Jun ; 34 (6) : 1065-1075. [epub] 20190121

Pediatr Nephrol
ISSN 1432-198X | 0931-041X
Source

Language English Country Germany Media print-electronic

Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid30666461

PubMed 30666461
DOI 10.1007/s00467-018-4188-8
PII: 10.1007/s00467-018-4188-8
Knihovny.cz E-resources

Keywords
Cystic kidney disease, GFR decline, HNF1B, Hypomagnesemia, MODY,
MeSH
Kidney Failure, Chronic genetics MeSH
Child MeSH
Phenotype MeSH
Genetic Association Studies MeSH
Hepatocyte Nuclear Factor 1-beta genetics MeSH
Infant MeSH
Humans MeSH
Adolescent MeSH
Infant, Newborn MeSH
Polycystic Kidney Diseases genetics pathology physiopathology MeSH
Child, Preschool MeSH
Disease Progression MeSH
Registries MeSH
Age of Onset MeSH
Check Tag
Child MeSH
Infant MeSH
Humans MeSH
Adolescent MeSH
Male MeSH
Infant, Newborn MeSH
Child, Preschool MeSH
Female MeSH
Publication type
Journal Article MeSH
Multicenter Study MeSH
Research Support, Non-U.S. Gov't MeSH
Geographicals
Germany MeSH
Names of Substances
Hepatocyte Nuclear Factor 1-beta MeSH
HNF1B protein, human MeSH Browser

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