Case Report: Nephrocalcinosis from pancreatic hypoplasia in HNF1B disease: a multigenerational expression with genetic confirmation in the youngest generation

Naga Sumanth Reddy Gopireddy; Sahil Grover; Imran Khawaja; Mohamed Fawzi Mudarres; Prerna Rastogi; Maria Story; Christie P Thomas

doi:10.3389/fmed.2025.1671893

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Case Report: Nephrocalcinosis from pancreatic hypoplasia in HNF1B disease: a multigenerational expression with genetic confirmation in the youngest generation

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Case Report: Nephrocalcinosis from pancreatic hypoplasia in HNF1B disease: a multigenerational expression with genetic confirmation in the youngest generation

Naga Sumanth Reddy Gopireddy, Sahil Grover, Imran Khawaja, Mohamed Fawzi Mudarres, Prerna Rastogi, Maria Story and Christie P Thomas

Frontiers in medicine, Vol.12, 1671893

2026

DOI: 10.3389/fmed.2025.1671893

PMCID: PMC12903773

PMID: 41694676

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Abstract

HNF1B-associated disease is a genetic disorder caused by heterozygous pathogenic variants in the HNF1B gene, leading to a variety of clinical phenotypes primarily affecting the kidneys, pancreas, liver, and genitourinary tract. First identified in 1997 as the cause of MODY5 (maturity-onset diabetes of the young, type 5), the disease spectrum has since expanded to include kidney disease, pancreatic hypoplasia, genital malformations, gout, hypomagnesemia, liver abnormalities, and primary hyperparathyroidism. Variable expressivity and limited penetrance complicate diagnosis, with some individuals presenting without the classical features of partial pancreatic hypoplasia, renal developmental abnormalities or MODY. Genetic testing remains crucial for accurate diagnosis, especially in families with varied phenotypic expressions. The index case, a 53-year-old woman, presented with hyperoxaluria, advanced chronic kidney disease (CKD), bilateral nephrocalcinosis, and pancreatic hypoplasia. Family members demonstrated diverse features, including renal cysts, kidney stones, diabetes, and pancreatic dysfunction. Genetic testing confirmed a pathogenic HNF1B variant (C295R) in the youngest family member, reinforcing the hereditary nature of the condition. This case report highlights the variable clinical presentation of HNF1B nephropathy across generations, illustrating the multisystem nature of the disease and emphasizing the importance of genetic testing for diagnosis and family screening.

maturity-onset diabetes of the young (MODY)

HNF1B mutation

hyperoxaluria

nephrocalcinosis

genetic kidney disease

renal cysts and diabetes syndrome (RCAD)

chronic kidney disease (CKD)

pancreatic hypoplasia

Details

Title: Subtitle: Case Report: Nephrocalcinosis from pancreatic hypoplasia in HNF1B disease: a multigenerational expression with genetic confirmation in the youngest generation
Creators: Naga Sumanth Reddy Gopireddy - University of Iowa
Sahil Grover - University of Iowa
Imran Khawaja - University of Iowa
Mohamed Fawzi Mudarres - University of Iowa
Prerna Rastogi - University of Iowa
Maria Story
Christie P Thomas - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in medicine, Vol.12, 1671893
DOI: 10.3389/fmed.2025.1671893
PMID: 41694676
PMCID: PMC12903773
NLM abbreviation: Front Med (Lausanne)
ISSN: 2296-858X
eISSN: 2296-858X
Publisher: Frontiers Media
Language: English
Date published: 2026
Academic Unit: Physician Assistant Studies; Stead Family Department of Pediatrics; Pathology; Obstetrics and Gynecology; Nephrology; Internal Medicine
Record Identifier: 9985139316002771

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