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

Lara Rodríguez‐Laguna; Kristina Ibáñez; Gema Gordo; Sixto García‐Miñáur; Fernando Santos‐Simarro; Noelia Agrá; Elena Vallespín; Victoria E. F. Montaño; Rubén Martín‐Arenas; Ángela del Pozo; Héctor González-Pecellín; Rocío Mena; Inmaculada Rueda‐Arenas; María Vanessa Pérez-Gómez; Cristina Villaverde; Ana Bustamante; Carmen Ayuso; Víctor L. Ruiz‐Pérez; Julián B. Nevado; Pablo Daniel Lapunzina; Juan Carlos López‐Gutiérrez; Víctor Martínez‐Glez

doi:10.1038/gim.2017.200

GeneticsGenetics in MedicineFeb 15, 2018

Peer-reviewed journal article

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

Lara Rodríguez‐Laguna iD, Kristina Ibáñez iD, Gema Gordo iD, Sixto García‐Miñáur iD, Fernando Santos‐Simarro iD, Noelia Agrá, Elena Vallespín iD, Victoria E. F. Montaño, Rubén Martín‐Arenas iD, Ángela del Pozo iD, Héctor González-Pecellín, Rocío Mena iD, Inmaculada Rueda‐Arenas, María Vanessa Pérez-Gómez iD, Cristina Villaverde iD, Ana Bustamante, Carmen Ayuso iD, Víctor L. Ruiz‐Pérez iD, Julián B. Nevado iD, Pablo Daniel Lapunzina iD, Juan Carlos López‐Gutiérrez iD, Víctor Martínez‐Glez iD

Abstract

BackgroundCLAPO 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. Although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.\n\nSubjects and methodsWe clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from nine patients using high-throughput, deep sequencing.\n\nResultsWe identified five activating mutations in the PIK3CA gene in affected tissues from six of the nine patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.\n\nConclusionsWe 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.

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