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Link to original content: http://pubmed.ncbi.nlm.nih.gov/32860533/
Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon - PubMed Skip to main page content
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Review
. 2021 Mar;140(3):401-421.
doi: 10.1007/s00439-020-02219-2. Epub 2020 Aug 29.

Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon

Lisa Gianesello  1 , Dorella Del Prete  1 , Franca Anglani  2 , Lorenzo A Calò  1
Affiliations
Review

Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon

Lisa Gianesello et al. Hum Genet. 2021 Mar.

Abstract

Dent disease is a rare genetic proximal tubulopathy which is under-recognized. Its phenotypic heterogeneity has led to several different classifications of the same disorder, but it is now widely accepted that the triad of symptoms low-molecular-weight proteinuria, hypercalciuria and nephrocalcinosis/nephrolithiasis are pathognomonic of Dent disease. Although mutations on the CLCN5 and OCRL genes are known to cause Dent disease, no such mutations are found in about 25-35% of cases, making diagnosis more challenging. This review outlines current knowledge regarding Dent disease from another perspective. Starting from the history of Dent disease, and reviewing the clinical details of patients with and without a genetic characterization, we discuss the phenotypic and genetic heterogeneity that typifies this disease. We focus particularly on all those confounding clinical signs and symptoms that can lead to a misdiagnosis. We also try to shed light on a concealed aspect of Dent disease. Although it is a proximal tubulopathy, its misdiagnosis may lead to patients undergoing kidney biopsy. In fact, some individuals with Dent disease have high-grade proteinuria, with or without hematuria, as in the clinical setting of glomerulopathy, or chronic kidney disease of uncertain origin. Although glomerular damage is frequently documented in Dent disease patients' biopsies, there is currently no reliable evidence of renal biopsy being of either diagnostic or prognostic value. We review published histopathology reports of tubular and glomerular damage in these patients, and discuss current knowledge regarding the role of CLCN5 and OCRL genes in glomerular function.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Time line showing the main steps in the history of Dent disease
See this image and copyright information in PMC

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