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

Lisa T. Emrick, Lauren Murphy, Alireza A. Shamshirsaz, Rodrigo Ruano, Christopher I. Cassady, Liu Liu, Fengqi Chang, V. Reid Sutton, Marilyn Li, Ignatia B. Van den Veyver

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 ofDNAextracted from culturedamniotic cells, but not fromDNAdirectly 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.

Original languageEnglish (US)
Pages (from-to)2633-2637
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number10
DOIs
StatePublished - Jan 1 2014

Keywords

  • Lipomatous malformation
  • Mosaicism
  • Prenatal diagnosis
  • Somatic overgrowth
  • Vascular anomalies

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Emrick, L. T., Murphy, L., Shamshirsaz, A. A., Ruano, R., Cassady, C. I., Liu, L., Chang, F., Sutton, V. R., Li, M., & Van den Veyver, I. B. (2014). Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes. American Journal of Medical Genetics, Part A, 164(10), 2633-2637. https://doi.org/10.1002/ajmg.a.36672