HNF1B nephropathy has a slow-progressive phenotype in childhood

• Verfasst von: Okorn, Christine [VerfasserIn]
• Verfasst von: Tönshoff, Burkhard [VerfasserIn]
• Titel: HNF1B nephropathy has a slow-progressive phenotype in childhood
• Titelzusatz: with the exception of very early onset cases : results of the German Multicenter HNF1B Childhood Registry
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 21 January 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 25.11.2019
• Titel Quelle: Enthalten in: Pediatric nephrology
• Ort Quelle: Berlin : Springer, 1987
• Jahr Quelle: 2019
• Band/Heft Quelle: 34(2019), 6, Seite 1065-1075
• ISSN Quelle: 1432-198X
• DOI: doi:10.1007/s00467-018-4188-8
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cystic kidney disease
• Sach-SW: GFR decline
• Sach-SW: HNF1B
• Sach-SW: Hypomagnesemia
• Sach-SW: MODY
• K10plus-PPN: 168333051X

Abstract

BackgroundHNF1B 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.MethodsLongitudinal 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.ResultsEighty-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.ConclusionsIn 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.