29446767|t|CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. 29446767|a|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. 29446767 0 14 CLAPO syndrome disease MESH:C567763|BERN:262813101 29446767 53 59 PIK3CA gene MIM:171834|HGNC:8975|Ensembl:ENSG00000121879|BERN:324295302 29446767 133 147 CLAPO syndrome disease MESH:C567763|BERN:262813101 29446767 158 175 vascular disorder disease MESH:D014652|BERN:256572101 29446767 193 232 capillary malformation of the lower lip disease MESH:C567763|BERN:262813101 29446767 234 289 lymphatic malformation predominant on the face and neck disease MESH:C567763|BERN:262813101 29446767 589 594 CLAPO disease MESH:C567763|BERN:262813101 29446767 748 759 PIK3CA gene gene MIM:171834|HGNC:8975|Ensembl:ENSG00000121879|BERN:324295302 29446767 847 855 c.248T>C mutation CUI-less 29446767 857 867 p.Phe83Ser mutation CUI-less 29446767 906 929 developmental disorders disease BERN:257523801 29446767 1009 1025 PIK3CA mutations gene CUI-less 29446767 1043 1048 CLAPO disease MESH:C567763|BERN:262813101