CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype

• Published in: Genetics in medicine Vol. 20; no. 8; pp. 882 - 889
• Main Authors: Rodriguez-Laguna, Lara, Ibañez, Kristina, Gordo, Gema, Garcia-Minaur, Sixto, Santos-Simarro, Fernando, Agra, Noelia, Vallespín, Elena, Fernández-Montaño, Victoria E, Martín-Arenas, Rubén, del Pozo, Ángela, González-Pecellín, Héctor, Mena, Rocío, Rueda-Arenas, Inmaculada, Gomez, María V, Villaverde, Cristina, Bustamante, Ana, Ayuso, Carmen, Ruiz-Perez, Víctor L, Nevado, Julián, Lapunzina, Pablo, Lopez-Gutierrez, Juan C, Martinez-Glez, Victor
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2018; Elsevier Limited
• Subjects: Adolescent; Adult; Arteriovenous Malformations - genetics; Arteriovenous Malformations - physiopathology; Biomedical and Life Sciences; Biomedicine; Child; Class I Phosphatidylinositol 3-Kinases - genetics; Class I Phosphatidylinositol 3-Kinases - physiology; Female; Genetic Association Studies - methods; High-Throughput Nucleotide Sequencing - methods; Human Genetics; Humans; Laboratory Medicine; Lymphatic Diseases - genetics; Lymphatic Diseases - physiopathology; Male; Mutation; Phosphatidylinositol 3-Kinases - genetics; Retrospective Studies; somatic mosaicism; vascular malformation; CLAPO; PIK3CA; overgrowth
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1038/gim.2017.200

Purpose CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. Methods We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing. Results We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders. Conclusion We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.