Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS)

Exp Dermatol. 2016 Jan;25(1):17-9. doi: 10.1111/exd.12826. Epub 2015 Oct 13.

Abstract

Klippel-Trenaunay syndrome (KTS), originally described as a triad of cutaneous capillary malformation, bone and soft-tissue hypertrophy, as well as venous and lymphatic malformations, has been considered by dermatologists as a distinct diagnostic entity. However, cases with KTS have also been reported to have neurological disorders, developmental delay and digital abnormalities, indicating multisystem involvement. Recently, a number of overgrowth syndromes, with overlapping phenotypic features with KTS, have been identified; these include MCAP and CLOVES syndromes as well as fibroadipose hyperplasia. These conditions harbour mutations in the PIK3CA gene, and they have been included in the PIK3CA-related overgrowth spectrum (PROS). Based on recent demonstrations of PIK3CA mutations also in KTS, it appears that, rather than being a distinct diagnostic entity, KTS belongs to PROS. These observations have potential diagnostic and therapeutic implications for KTS.

Keywords: CLOVES syndrome; Klippel-Trenaunay syndrome; PIK3CA-related overgrowth spectrum; fibroadipose hyperplasia.

MeSH terms

  • Adipose Tissue / pathology
  • Cell Proliferation
  • Class I Phosphatidylinositol 3-Kinases
  • Humans
  • Hyperplasia
  • Klippel-Trenaunay-Weber Syndrome / classification
  • Klippel-Trenaunay-Weber Syndrome / diagnosis*
  • Klippel-Trenaunay-Weber Syndrome / genetics
  • Lipoma / classification
  • Lipoma / diagnosis*
  • Lipoma / genetics
  • Musculoskeletal Abnormalities / classification
  • Musculoskeletal Abnormalities / diagnosis*
  • Musculoskeletal Abnormalities / genetics
  • Mutation
  • Mutation, Missense
  • Nevus / classification
  • Nevus / diagnosis*
  • Nevus / genetics
  • Phenotype
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Malformations / classification
  • Vascular Malformations / diagnosis*
  • Vascular Malformations / genetics

Substances

  • MTOR protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Supplementary concepts

  • Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi