Background: 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. Although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism. Subjects and methods: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from nine patients using high-throughput, deep sequencing. Results: We 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. Conclusions: 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.

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