Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes

Am J Med Genet A. 2014 Oct;164A(10):2633-7. doi: 10.1002/ajmg.a.36672. Epub 2014 Jul 14.


Congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES) syndrome, a segmental overgrowth syndrome, is caused by post zygotic somatic mutations in PIK3CA, a gene involved in the receptor tyrosine kinase phosphatidylinositol 3-kinase (PI3)-AKT growth-signaling pathway. Prenatal ultrasound findings of lymphovascular malformations, segmental overgrowth and skeletal defects can raise suspicion for CLOVES syndrome, but molecular confirmation of PIK3CA mutations on prenatally obtained samples is challenging because of somatic mosaicism. We detected a mosaic disease-causing mutation in PIK3CA by sequencing of DNA extracted from cultured amniotic cells, but not from DNA directly prepared from an amniotic fluid sample in a fetus with prenatally suspected CLOVES syndrome. The infant was born prematurely and displayed severe lymphovascular malformations and segmental overgrowth consistent with a clinical diagnosis of CLOVES syndrome; he passed away at 29 days of life. We discuss the complexities and limitations of genetic testing for somatic mosaic mutations in the prenatal period and highlight the potential need for multiple approaches to arrive at a molecular diagnosis. © 2014 Wiley Periodicals, Inc.

Keywords: lipomatous malformation; mosaicism; prenatal diagnosis; somatic overgrowth; vascular anomalies.

Publication types

  • Case Reports

MeSH terms

  • Amniotic Fluid / cytology*
  • Class I Phosphatidylinositol 3-Kinases
  • Fetus / cytology
  • Humans
  • Infant, Newborn
  • Lipoma / genetics*
  • Musculoskeletal Abnormalities / genetics*
  • Mutation / genetics*
  • Nevus / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prenatal Diagnosis / methods
  • Signal Transduction / genetics
  • Vascular Malformations / genetics*


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

Supplementary concepts

  • Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi