Kidney Week

Abstract: SA-PO592

Unmasking the Mimickers: HNF1B Variants in Pediatric Kidney Diseases

Session Information

• Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Salcedo-Giraldo, Jordy, Children's National Hospital, Washington, District of Columbia, United States

Jordy Salcedo-Giraldo, MD

• Wink, Krista Renee, Children's National Hospital, Washington, District of Columbia, United States

Krista Renee Wink

• Freiman, Andrew, Children's National Hospital, Washington, District of Columbia, United States

Andrew Freiman, MS

• Pyle, Louise C., Children's National Hospital, Washington, District of Columbia, United States

Louise C. Pyle, MD, PhD

• Gulati, Ashima, Children's National Hospital, Washington, District of Columbia, United States

Ashima Gulati, MD, PhD, FASN

Introduction

Hepatocyte nuclear factor 1 beta (HNF1B) variants are associated with a spectrum of phenotypic manifestations including renal, pancreatic, and metabolic disorders. These variants can pose diagnostic dilemmas due to their diverse clinical presentations, often mimicking other congenital kidney conditions.

Case Description

A retrospective case series of 12 pediatric patients (age 4 months to 10 years) referred to our Renal Genetics Clinic with varied kidney phenotypic findings ultimately attributed to heterozygous disease-causing HNF1B variants. Each case exhibited unique clinical features, including cystic and non-cystic renal abnormalities, early-onset diabetes, and abnormal liver tests. Table 1 lists the clinical, laboratory, and kidney imaging findings at clinical presentation. Genetic investigation revealed two types of HNF1B defects: (i) whole gene deletion (67%); and (ii) truncating or missense variant predicted to be pathogenic (33%), which were de novo in all cases but one.

Discussion

Our findings highlight the importance of considering HNF1B variants in the differential diagnosis of pediatric patients presenting with structural kidney abnormalities with or without cystic kidney disease or specific multisystemic features. Despite disparate presentations, the genetic evaluation revealed a unifying etiology in all cases. Enhanced awareness of the protean nature of HNF1B-related disorders is valuable for accurate prognostication and optimization of multidisciplinary management strategies.

Table 1

Key: Cystic = cystic renal disease, Non-Cystic = non-cystic/functional renal disease, Abn LFT = abnormal liver test, DM = diabetes, ↓ Mg = hypomagnesemia, ↑ U = hyperuricemia, GD = growth delay, FH = family history