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

BACKGROUND: 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.

CASE PRESENTATION: 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.

CONCLUSION: 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.