Mesenchymal Hamartoma of the Liver and DICER1 Syndrome

N Engl J Med. 2019 May 9;380(19):1834-1842. doi: 10.1056/NEJMoa1812169.


Mesenchymal hamartoma of the liver (MHL) is a benign tumor affecting children that is characterized by a primitive myxoid stroma with cystically dilated bile ducts. Alterations involving chromosome 19q13 are a recurrent underlying cause of MHL; these alterations activate the chromosome 19 microRNA cluster (C19MC). Other cases remain unexplained. We describe two children with MHLs that harbored germline DICER1 pathogenic variants. Analysis of tumor tissue from one of the children revealed two DICER1 "hits." Mutations in DICER1 dysregulate microRNAs, mimicking the effect of the activation of C19MC. Our data suggest that MHL is a new phenotype of DICER1 syndrome. (Funded by the Canadian Institutes of Health Research and others.).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Chromosomes, Human, Pair 19*
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Hamartoma / diagnostic imaging
  • Hamartoma / genetics*
  • Hamartoma / pathology
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Diseases / diagnostic imaging
  • Liver Diseases / genetics*
  • Liver Diseases / pathology
  • Male
  • Mesoderm
  • MicroRNAs / metabolism*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Pedigree
  • Phenotype
  • Ribonuclease III / genetics*


  • MicroRNAs
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

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