Somatic PIK3CA mutations in seven patients with PIK3CA-related overgrowth spectrum

Am J Med Genet A. 2017 Apr;173(4):978-984. doi: 10.1002/ajmg.a.38105.

Abstract

Somatic mutations in PIK3CA cause many overgrowth syndromes that have been recently coined the "PIK3CA-Related Overgrowth Spectrum." Here, we present seven molecularly confirmed patients with PIK3CA-Related Overgrowth Spectrum, including patients with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome, Klippel-Trenaunay syndrome, lymphatic malformation and two with atypical phenotypes that cannot be classified into existing disease categories. The literature on PIK3CA-Related Overgrowth Spectrum, suggests that PIK3CA c.1258T>C; p.(Cys420Arg), c.1624G>A; p.(Glu542Lys), c.1633G>A; p.(Glu545Lys), c.3140A>G; p.(His1047Arg), and c.3140A>T; p.(His1047Leu) can be identified in approximately 90% of patients without brain overgrowth. Therefore, droplet digital polymerase chain reaction targeting these mutation hotspots could be used as the first-tier genetic test on patients with PIK3CA-Related Overgrowth Spectrum who do not have signs of overgrowth in their central nervous system. © 2017 Wiley Periodicals, Inc.

Keywords: PIK3CA; PIK3CA-related overgrowth spectrum; somatic mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Female
  • Gene Expression
  • Genetic Association Studies
  • Genetic Testing
  • Humans
  • Klippel-Trenaunay-Weber Syndrome / diagnosis
  • Klippel-Trenaunay-Weber Syndrome / genetics*
  • Klippel-Trenaunay-Weber Syndrome / pathology
  • Male
  • Mutation*
  • Nevus / diagnosis
  • Nevus / genetics*
  • Nevus / pathology
  • Phenotype
  • Polymerase Chain Reaction / methods
  • Scoliosis / diagnosis
  • Scoliosis / genetics*
  • Scoliosis / pathology
  • Vascular Malformations / diagnosis
  • Vascular Malformations / genetics*
  • Vascular Malformations / pathology

Substances

  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human

Supplementary concepts

  • Epidermal Nevus