. 2018 Dec;33(12):2281-2288.

doi: 10.1007/s00467-018-4040-1. Epub 2018 Sep 3.

Structural renal abnormalities in the DICER1 syndrome: a family-based cohort study

Nicholas E Khan^{1

2}, Alexander Ling³, Molly E Raske⁴, Laura A Harney⁵, Ann G Carr⁵, Amanda Field⁶, Anne K Harris^{7

8

9}, Gretchen M Williams^{7

8}, Louis P Dehner¹⁰, Yoav H Messinger^{7

8}, D Ashley Hill^{6

11}, Kris Ann P Schultz^{7

8

9}, Douglas R Stewart¹²

Affiliations

¹ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20850, USA.
² Rush Medical College, Chicago, IL, 60612, USA.
³ Clinical Center Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, 20892, USA.
⁴ Department of Radiology, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁵ Westat, Inc., Rockville, MD, 20850, USA.
⁶ Division of Pathology and Center for Clinical and Immunology Research, Children's National Health System, Washington, DC, 20010, USA.
⁷ Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁸ International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, MN, 55404, USA.
⁹ International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, MN, 55404, USA.
¹⁰ Department of Pathology and Immunology, Washington University Medical Center, St. Louis, MO, 63130, USA.
¹¹ Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
¹² Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20850, USA. drstewart@mail.nih.gov.

PMID: 30178239
PMCID: PMC6203641
DOI: 10.1007/s00467-018-4040-1

Structural renal abnormalities in the DICER1 syndrome: a family-based cohort study

Nicholas E Khan et al. Pediatr Nephrol. 2018 Dec.

. 2018 Dec;33(12):2281-2288.

doi: 10.1007/s00467-018-4040-1. Epub 2018 Sep 3.

Authors

Affiliations

¹ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20850, USA.
² Rush Medical College, Chicago, IL, 60612, USA.
³ Clinical Center Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, 20892, USA.
⁴ Department of Radiology, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁵ Westat, Inc., Rockville, MD, 20850, USA.
⁶ Division of Pathology and Center for Clinical and Immunology Research, Children's National Health System, Washington, DC, 20010, USA.
⁷ Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN, 55404, USA.
⁸ International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, MN, 55404, USA.
⁹ International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, MN, 55404, USA.
¹⁰ Department of Pathology and Immunology, Washington University Medical Center, St. Louis, MO, 63130, USA.
¹¹ Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
¹² Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20850, USA. drstewart@mail.nih.gov.

PMID: 30178239
PMCID: PMC6203641
DOI: 10.1007/s00467-018-4040-1

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Collecting system; DICER1; Kidney; Renal cyst; Structural abnormality.

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Conflict of interest statement

Disclosure of Financial Interests and Conflicts of Interest. None.

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Structural renal abnormalities in the DICER1 syndrome: a family-based cohort study

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Structural renal abnormalities in the DICER1 syndrome: a family-based cohort study

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