RT Journal Article SR Electronic T1 Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies JF Clinical Journal of the American Society of Nephrology JO CLIN J AM SOC NEPHROL FD American Society of Nephrology SP 1974 OP 1983 DO 10.2215/CJN.01280217 VO 12 IS 12 A1 König, Jens A1 Kranz, Birgitta A1 König, Sabine A1 Schlingmann, Karl Peter A1 Titieni, Andrea A1 Tönshoff, Burkhard A1 Habbig, Sandra A1 Pape, Lars A1 Häffner, Karsten A1 Hansen, Matthias A1 Büscher, Anja A1 Bald, Martin A1 Billing, Heiko A1 Schild, Raphael A1 Walden, Ulrike A1 Hampel, Tobias A1 Staude, Hagen A1 Riedl, Magdalena A1 Gretz, Norbert A1 Lablans, Martin A1 Bergmann, Carsten A1 Hildebrandt, Friedhelm A1 Omran, Heymut A1 Konrad, Martin YR 2017 UL http://cjasn.asnjournals.org/content/12/12/1974.abstract 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.