Extrarenal Clinical Features are Reported for Most Genes Implicated in Genetic Kidney Disease

Introduction: Genetic kidney disease is often suspected based on a family history of the disease or the presence of extrarenal features. This study examined how often a positive family history or syndromic features are found. Methods: A total of 255 genes from the Genomics England “green” lists for...

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Bibliographic Details
Main Authors: Benjamin Serrano, Judy Savige
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925000701
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Summary:Introduction: Genetic kidney disease is often suspected based on a family history of the disease or the presence of extrarenal features. This study examined how often a positive family history or syndromic features are found. Methods: A total of 255 genes from the Genomics England “green” lists for congenital anomalies of the kidney and urinary tract (CAKUT) (n = 57), ciliopathies and cystic kidney diseases (n = 90), hematuria (n = 5), renal proteinuria (n = 55), and renal tubulopathies (n = 48) were examined for mode of inheritance and, in the Online Mendelian Inheritance in Man (OMIM), for reported clinical features in different systems (neurological, cardiac, etc.) that would be obvious on a history or physical examination. Results: Autosomal recessive (AR) inheritance was recorded for 148 of the 248 genes (60%) with an OMIM entry. Extrarenal features were associated with 221 genes (89%), including those causing hematuria (5, 100%), renal ciliopathies (86, 97%), CAKUT (52, 91%), renal tubulopathies (41, 85%), and proteinuric renal diseases (37, 76%).The median number of affected systems was 4 (range: 0–10). More extrarenal features were associated with CAKUT (4, 0–10) and the ciliopathies (5, 0–9) than with hematuria (2, 2–5), proteinuria (3, 0–7), and the tubulopathies (3, 0–7) (P < 0.00001). The most commonly-affected systems were growth and musculoskeletal (164, 66%), neurological (147, 59%), and ocular (133, 54%). Conclusion: Extrarenal associations have been reported for most genes affected in genetic kidney disease, and are more common with pediatric-onset conditions with recessive inheritance. However, information is limited for how often extrarenal features are found in any individual.
ISSN:2468-0249