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.