PT  - JOURNAL ARTICLE
AU  - König, Jens
AU  - Kranz, Birgitta
AU  - König, Sabine
AU  - Schlingmann, Karl Peter
AU  - Titieni, Andrea
AU  - Tönshoff, Burkhard
AU  - Habbig, Sandra
AU  - Pape, Lars
AU  - Häffner, Karsten
AU  - Hansen, Matthias
AU  - Büscher, Anja
AU  - Bald, Martin
AU  - Billing, Heiko
AU  - Schild, Raphael
AU  - Walden, Ulrike
AU  - Hampel, Tobias
AU  - Staude, Hagen
AU  - Riedl, Magdalena
AU  - Gretz, Norbert
AU  - Lablans, Martin
AU  - Bergmann, Carsten
AU  - Hildebrandt, Friedhelm
AU  - Omran, Heymut
AU  - Konrad, Martin
ED  - , 
TI  - Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies
AID  - 10.2215/CJN.01280217
DP  - 2017 Dec 07
TA  - Clinical Journal of the American Society of Nephrology
PG  - 1974--1983
VI  - 12
IP  - 12
4099  - http://cjasn.asnjournals.org/content/12/12/1974.short
4100  - http://cjasn.asnjournals.org/content/12/12/1974.full
SO  - CLIN J AM SOC NEPHROL2017 Dec 07; 12
AB  - Background and objectives Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (NPHP1 to -20) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD.Design, setting, participants, & measurements We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5±6.1 years.Results In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affecting NPHP genes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygous NPHP1 deletion was, by far, the most frequent genetic defect (n=60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for the NPHP1 group and 66% [61 of 92] for children without NPHP1). A homozygous NPHP1 deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carrying NPHP1 mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4±2.4 years. In contrast within the non-NPHP1 group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood.Conclusions Mutations in NPHP genes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.