Identification of aggressive Gardner syndrome phenotype associated with a de novo APC variant, c.4666dup

Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2):a003640. doi: 10.1101/mcs.a003640. Print 2019 Apr.

Abstract

Gardner syndrome describes a variant phenotype of familial adenomatous polyposis (FAP), primarily characterized by extracolonic lesions including osteomas, dental abnormalities, epidermal cysts, and soft tissue tumors. We describe a 2-yr-old boy presenting with a 2-cm soft tissue mass of the forehead. Pathologic evaluation revealed a nuchal-type/Gardner-associated fibroma. Sequencing of the APC gene revealed a pathologic variant c.4666dupA. Parental sequencing of both blood and buccal tissue supported the de novo occurrence of this pathologic variant. Further imaging revealed a number of additional lesions including a large lumbar paraspinal desmoid, a 1-cm palpable lesion posterior to the left knee, firm lesions on bilateral heels, and multiple subdermal lesions. Colonoscopy was negative. This case illustrates a genetic variant of Gardner syndrome resulting in an aggressive early childhood phenotype and highlights the need for an individualized approach to treatment.

Keywords: desmoid tumors; facial neoplasm; intestinal polyp; neoplasm of the gastrointestinal tract; neoplasm of the large intestine.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Child, Preschool
  • Forehead / diagnostic imaging
  • Forehead / pathology*
  • Gardner Syndrome / genetics
  • Gardner Syndrome / pathology*
  • Genetic Variation
  • Heel / diagnostic imaging
  • Heel / pathology*
  • Humans
  • Knee / diagnostic imaging
  • Knee / pathology*
  • Male
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA
  • Tumor Burden

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein