HNF1β-Kidney Disease: Case Series

Introduction: We describe a series of four patients with mutations in the HNF1β gene and varied renal manifestations followed at Weill Cornell Pediatric Nephrology clinic. Case Description: Patient 1 is an 8-year-old male whose prenatal ultrasound showed echogenic kidneys, confirmed postnatally, also with calyceal dilation. His estimated GFR is currently 59 mL/min/1.73m2 (Stage 2 CKD). Genetic testing demonstrated a heterozygous p.F236I (c.706 T>A) variant in the HNF1β gene. He has no extrarenal manifestations including normal hemoglobin A1c and has no family history of HNF1β. Patient 2 is a 9-month-old female whose prenatal ultrasound demonstrated mild pelviectasis and a small cyst on the left kidney. Postnatal ultrasound showed echogenic kidneys with bilateral renal cysts. She has normal serum creatinine and no significant extrarenal manifestations. Genetic testing was positive for pathogenic, heterozygous mutation in HNF1 β gene; whole gene deletion. She has no family history of renal disease. Patient 3 is a 4-year-old female who presented prenatally with ultrasound demonstrating echogenic kidneys. Postnatal ultrasound showed bilateral cysts. She has normal renal function, but has a known family history of HNF1β-renal disease: her mother has a history of renal cysts, gout, proteinuria, and hypomagnesemia. Genetic testing showed a heterozygous autosomal dominant HNF1β pathogenic variant, c.487C>T, p.(Q163*). She has no extrarenal manifestations. Patient 4 is an 18-year-old male, who is most significantly affected by HNF1β. He presented to our clinic at 14 following kidney transplant performed at 3. He is now post his second deceased donor kidney transplant. He was diagnosed with Mature Onset Diabetes of the Young (MODY) at 8—consistent with Renal Cysts and Diabetes Syndrome (RCAD), insulin dependent. Genetic testing showed a heterozygous autosomal dominant variant in HNF1β (c.541 C>T, p.(R181*). He also has a history of elevated liver enzymes. His father has an atrophic kidney and insulin dependent diabetes but does not have genetic confirmation. Discussion: The four patients with HNF1β-disease have varied renal manifestations ranging from renal cysts with normal kidney function, to ESKD. Three patients have no significant extrarenal manifestations at this time, however one has MODY. Thus, HNF1β-disease may have significant phenotypic variation. Careful renal surveillance and diabetes screening is warranted in these patients.