Stokman, MF;
van der Zwaag, B;
van de Kar, NCAJ;
van Haelst, MM;
van Eerde, AM;
van der Heijden, JW;
Kroes, HY;
... Lilien, MR; + view all
(2018)
Clinical and genetic analyses of a Dutch cohort of 40 patients with a nephronophthisis-related ciliopathy.
Pediatric Nephrology
, 33
(10)
pp. 1701-1712.
10.1007/s00467-018-3958-7.
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Abstract
BACKGROUND: Nephronophthisis is an autosomal recessive ciliopathy and important cause of end-stage renal disease (ESRD) in children and young adults. Diagnostic delay is frequent. This study investigates clinical characteristics, initial symptoms, and genetic defects in a cohort with nephronophthisis-related ciliopathy, to improve early detection and genetic counseling. METHODS: Forty patients from 36 families with nephronophthisis-related ciliopathy were recruited at university medical centers and online. Comprehensive clinical and genotypic data were recorded. Patients without molecular diagnosis were offered genetic analysis. RESULTS: Of 40 patients, 45% had isolated nephronophthisis, 48% syndromic diagnosis, and 7% nephronophthisis with extrarenal features not constituting a recognizable syndrome. Patients developed ESRD at median 13 years (range 5–47). Median age of symptom onset was 9 years in both isolated and syndromic forms (range 5–26 vs. 5–33). Common presenting symptoms were fatigue (42%), polydipsia/polyuria (33%), and hypertension (21%). Renal ultrasound showed small-to-normal-sized kidneys, increased echogenicity (65%), cysts (43%), and abnormal corticomedullary differentiation (32%). Renal biopsies in eight patients showed nonspecific signs of chronic kidney disease (CKD). Twenty-three patients (58%) had genetic diagnosis upon inclusion. Thirteen of those without a genetic diagnosis gave consent for genetic testing, and a cause was identified in five (38%). CONCLUSIONS: Nephronophthisis is genetically and phenotypically heterogeneous and should be considered in children and young adults presenting with persistent fatigue and polyuria, and in all patients with unexplained CKD. As symptom onset can occur into adulthood, presymptomatic monitoring of kidney function in syndromic ciliopathy patients should continue until at least age 30.
| Type: | Article |
|---|---|
| Title: | Clinical and genetic analyses of a Dutch cohort of 40 patients with a nephronophthisis-related ciliopathy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00467-018-3958-7 |
| Publisher version: | https://doi.org/10.1007/s00467-018-3958-7 |
| Language: | English |
| Additional information: | © The Author(s) 2018. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Nephronophthisis, Pediatric kidney disease, Ciliopathy, Clinical registry, Gene-phenotype association |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10065015 |
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