Structural renal abnormalities in the DICER1 syndrome: a family-based cohort study
The DICER1 syndrome is a tumor-predisposition disorder caused by germline pathogenic variation in DICER1 and is associated with cystic nephroma and other renal neoplasms. Dicer1 mouse and rare human DICER1 syndrome case reports describe structural kidney and collecting system anomalies. We investigated renal function and the frequency of structural abnormalities of the kidney and collecting system in individuals with germline loss-of-function variants in DICER1.
In this family-based cohort study, prospectively ascertained germline DICER1-mutation carriers (DICER1-carriers) and unaffected family controls were evaluated at the National Institutes of Health Clinical Center with renal ultrasound and comprehensive laboratory testing. Two radiologists reviewed the imaging studies from all participants for structural abnormalities, cysts, and tumors.
Eighty-nine DICER1-carriers and 61 family controls were studied. Renal cysts were detected in 1/33 DICER1-carrier children without history of cystic nephroma. Similar proportions of adult DICER1-carriers (8/48; 17%) and controls (11/50; 22%) had ultrasound-detected renal cysts (P = 0.504). 8/89 (9%) DICER1-carriers harbored ultrasound-detected structural abnormalities of varying severity within the collecting system or kidney, nephrolithiasis, or nephrocalcinosis. None of the family controls (0/61) had similar findings on ultrasound (P = 0.02). No meaningful differences in renal laboratory values between DICER1-carriers and unaffected family controls were observed.
Our report is the first to systematically characterize renal function and anatomy in a large prospective cohort of DICER1-carriers and DICER1-negative family controls. DICER1-carriers may be at increased risk of structural anomalies of the kidney or collecting system. The role for DICER1 in renal morphogenesis merits additional investigation.
KeywordsDICER1 Kidney Structural abnormality Collecting system Renal cyst
The authors wish to thank the Pine Tree Apple Tennis Classic and St. Baldrick’s Foundation for their ongoing support of children’s cancer research. The authors also wish to thank the many patients, families, and treating physicians who participate in the NCI DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome study, the International OTST Registry, and/or the International Pleuropulmonary Blastoma/DICER1 Registry. We thank Rosamma Decastro, CRNP for clinical contributions.
This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute (NCI), Bethesda, MD. DAH is supported by NCI 2R01CA143167.
Compliance with ethical standards
All participants provided written, informed consent, and the study was approved by the National Cancer Institute’s Institutional Review Board (IRB). In addition, clinical, radiographic, and genetic data on participants enrolled in the International Pleuropulmonary/DICER1 Registry and the International Ovarian and Testicular Stromal Tumor Registry were abstracted and reviewed. Both registries are overseen by the IRB at Children’s Minnesota (protocols 98107, 0909-082, 1111-112). Participants in both registries provided informed, written consent for use of their registry data in the current analysis. The study adhered to the precepts in the Declaration of Helsinki.
Conflict of interest
The authors declare that they have no conflict of interest.
The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.
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