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.