Fetal anomalies associated with HNF1B mutations: report of 20 autopsy cases

Prenat Diagn. 2016 Aug;36(8):744-51. doi: 10.1002/pd.4858. Epub 2016 Jul 6.

Abstract

Objectives: To describe macroscopic and microscopic anomalies present in fetuses carrying hepatocyte nuclear factor-1 β mutation, their frequency, and genotype/phenotype correlations.

Methods: Clinical data, ultrasound findings, genetic studies, and autopsy reports of 20 fetal autopsies were analyzed. Histology was reviewed by two pathologists.

Results: Macroscopic findings were typically unilateral or bilateral renal enlargement and cortical cysts. Renal lesions were associated with congenital anomalies of the kidney and urinary tract in 25% of cases. Microscopic renal anomalies were dominated by glomerulocystic kidney and renal dysplasia. Extra-renal manifestations such as pancreatic hypoplasia (75%) and genital anomalies (68%) were only detected at autopsy. In 40% of cases, there was heterozygous deletion of the whole gene. There were de novo mutations in 40%.

Conclusion: This study underlines the importance of considering hepatocyte nuclear factor-1 β mutations in fetuses with congenital anomalies of the kidney and urinary tract, especially when associated with pancreatic hypoplasia. No correlation between phenotype and genotype was found, highlighting high intra-familial variability in cases with inherited mutations. © 2016 John Wiley & Sons, Ltd.

MeSH terms

  • Autopsy
  • Congenital Abnormalities / diagnostic imaging
  • Congenital Abnormalities / genetics
  • Congenital Abnormalities / pathology
  • Female
  • Genotype
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Kidney / abnormalities*
  • Kidney / diagnostic imaging
  • Kidney / pathology
  • Male
  • Mutation
  • Pancreas / abnormalities*
  • Pancreas / diagnostic imaging
  • Pancreatic Diseases / congenital*
  • Pancreatic Diseases / diagnostic imaging
  • Pancreatic Diseases / genetics
  • Phenotype
  • Pregnancy
  • Ultrasonography, Prenatal
  • Urogenital Abnormalities / diagnostic imaging
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology

Substances

  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta

Supplementary concepts

  • Pancreatic Agenesis, Congenital