title: Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes.
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 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Emrick
authors.forename: Lauren
authors.initials: L
authors.lastname: Murphy
authors.forename: Alireza A
authors.initials: AA
authors.lastname: Shamshirsaz
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ruano
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Cassady
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Fengqi
authors.initials: F
authors.lastname: Chang
authors.forename: V Reid
authors.initials: VR
authors.lastname: Sutton
authors.forename: Marilyn
authors.initials: M
authors.lastname: Li
authors.forename: Ignatia B
authors.initials: IB
authors.lastname: Van den Veyver
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D058534:Class I Phosphatidylinositol 3-Kinases; D005333:Fetus / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D008067:Lipoma / Q000235:genetics*; D009139:Musculoskeletal Abnormalities / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009506:Nevus / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D054079:Vascular Malformations / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: lipomatous malformation; mosaicism; prenatal diagnosis; somatic overgrowth; vascular anomalies