Bilaterally Enlarged Echogenic and Cystic Fetal Kidneys: HNF1B-Related Disease in the Differential Diagnosis
Year: 2026
Type: article
Study design: Case Report
Abstract: Bilaterally enlarged hyperechogenic fetal kidneys with visible cysts represent a diagnostically challenging phenotype that may occur in hepatocyte nuclear factor 1 homeobox B (HNF1B)-related disease, autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), renal dysplasia, and other developmental or cystic kidney disorders.We describe a fetus identified at 22 weeks' gestation with progressive bilateral nephromegaly, markedly increased renal echogenicity, reduced corticomedullary differentiation, and multiple small cortical/subcapsular cysts, with preserved bladder filling, amniotic fluid volume, fetal growth, and no major extrarenal abnormalities.Chromosomal microarray analysis (CMA) demonstrated no pathogenic copy-number abnormality, including deletion of the HNF1B-containing 17q12 region.Subsequent trio genomic sequencing identified a heterozygous pathogenic HNF1B nonsense variant, NM_000458.4:c.826C>T(p.Arg276Ter).The same variant was unexpectedly identified in the clinically asymptomatic mother, whose subsequent evaluation revealed subtle renal abnormalities and hypomagnesemia, illustrating marked intrafamilial variable expressivity.The infant was delivered at term with preserved urine output; postnatal imaging reproduced the prenatal renal phenotype, and follow-up demonstrated mild renal dysfunction and hypomagnesemia.Importantly, visible fetal renal cysts are a morphologic finding rather than a molecular diagnosis: Cysts may occur in HNF1B-related disease, ADPKD, ARPKD, and renal dysplasia, although conspicuous macrocysts are not typically the dominant early prenatal feature of classic ARPKD.The subsequent behavior of cysts in HNF1B-related disease also should not be assumed to follow the progressive cyst-expansion paradigm of ADPKD, because cyst burden may remain stable in many affected children and renal morphology may evolve variably over time.This case demonstrates the complementary roles of detailed fetal phenotyping, CMA, sequence analysis, parental testing, and longitudinal surveillance and emphasizes that molecular diagnosis establishes etiology but does not reliably predict renal progression or overall phenotypic severity.
Source: Newborn
Institutions: University of Calgary, Alberta Health Services
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7223380605