{Reference Type}: Journal Article
{Title}: Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies.
{Author}: König J;Kranz B;König S;Schlingmann KP;Titieni A;Tönshoff B;Habbig S;Pape L;Häffner K;Hansen M;Büscher A;Bald M;Billing H;Schild R;Walden U;Hampel T;Staude H;Riedl M;Gretz N;Lablans M;Bergmann C;Hildebrandt F;Omran H;Konrad M; ;
{Journal}: Clin J Am Soc Nephrol
{Volume}: 12
{Issue}: 12
{Year}: Dec 2017 7
{Factor}: 10.614
{DOI}: 10.2215/CJN.01280217
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Mutations in NPHP genes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.