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

TL;DR

This case report describes a family with a genetic disorder caused by a mutation in the HNF1B gene, showing varied symptoms across generations and highlighting the need for genetic testing.

Contribution

The report confirms the hereditary nature of HNF1B disease in a multigenerational family through genetic testing in the youngest member.

Findings

HNF1B disease presents with variable symptoms including kidney and pancreatic issues across multiple generations.

Genetic testing confirmed the HNF1B mutation in the youngest family member, aiding diagnosis and family screening.

The case illustrates the multisystem impact of HNF1B-associated disease beyond classical features.

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.

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