Table 1.
Clinical information and all (likely) pathogenic mutations and mutant allele frequencies identified in the prospective and retrospective cohorts are listed (with the exception of the 80 PIK3CA mutations, see Supporting Information Table S1)
| Gene | Identified variant(s) | Variant allele frequency (%) | Age/sex | Site | Clinical features | Histology |
|---|---|---|---|---|---|---|
| Prospective panel | ||||||
| GNA11 | c.627G > C (p.Gln209His) | 9 | 64/m | Hand | Unknown | Veno‐capillary malformation |
| GNA11 | c.547C > T (p.Arg183Cys) | 5 | 61/m | Upper eyelid | Congenital port wine stain; progressive hypertrophy | Veno‐capillary malformation |
| GNA11 | c.626A > T (p.Gln209Leu) | 3 | 72/m | Acetabulum | Unknown | Veno‐capillary malformation |
| GNAQ | c.548G > A (p.Arg183Gln) | 8 | 67/f | Skin neck | Residue after venous malformation | Veno‐capillary malformation |
| GNAQ | c.627A > C (p.Gln209His) | 4 | 57/f | Arm | Atypical lesion; spectrum non‐involuted congenital hemangioma (NICH)/ venous malformation | Veno‐capillary malformation |
| GNAQ | c.548G > A (p.Arg183Gln) | 8 | 81/f | Lower lip | Port wine stain in Sturge Weber Syndrome | Combined vascular malformation |
| GNAQ | c.627A > C (p.Gln209His) | 18 | 64/f | Epidural | Epidural mass | Veno‐capillary malformation |
| GNAQ | c.548G > A (p.Arg183Gln) | 8 | 43/f | Upper lip | Port wine stain with firm hypertrophy; KTS spectrum | Venous malformation |
| GNAQ | c.626A > T (p.Gln209Leu) | 21 | 15/m | Skin clavicle | Non congenital vascular high flow lesion | Veno‐capillary malformation |
| AKT‐1 | c.49G > A (p.Glu17Lys) | 8 | 5/m | Saphenous vein | Congenital port wine stain of one leg with firm overgrowth; mild phenotype of Proteus. | Venous malformation |
| KRAS | c.35_38delinsCTCA (p.Gly12_Gly13delinsAlaHis) | 32 | 56/f | Flank | Vascularized tumor | Veno‐capillary malformation |
| KRAS | c.64C > A (p.Gln22Lys) | 22 | 32/m | Cheek | KTS‐spectrum with lymphedema and port‐wine stain leg and multiple vascular lesions left side face | Veno‐capillary malformation |
| KRAS | c.35G > C (p.Gly12Ala) | 18 | 32/m | Cheek | Lipoma with vascular lesion | Venous malformation |
| KRAS | c.436G > A (p.Ala146Thr) | 17 | 45/f | Arm | KTS spectrum with venolymphatic lesion and port wine stain | Venous malformation |
| KRAS | c.37G > T (p.Gly13Cys) | 2 | 8/f | Lower jaw | Unknown | Veno‐capillary malformation |
| KRAS | c.35G > A (p.Gly12Asp) | 9 | 70/f | Subcutis buttock | Unknown | Veno‐capillary malformation |
| NRAS | c.182A > G (p.Gln61Arg) | 14 | 12/m | Thoracal skin | Multiple eruptive pyogenic granuloma | Capillary malformation |
| IDH1 | c.394C > T (p.Arg132Cys) | 2 | 12/f | Upper arm muscle | Venous malformation or non‐involuted congenital hemangioma | Veno‐capillary malformation |
| IDH1 | c.394C > T (p.Arg132Cys) | 14 | 38/f | Foot | Unknown | SCH |
| IDH1 | c.394C > T (p.Arg132Cys) | 10 | 15/m | Soft tissue foot | Unknown | SCH |
| PIK3CA; GNAQ | c.3140A > G (p.His1047Arg); c.627A > C (p.Gln209His) | 26; 26 | 53/m | Skull/dura | Vascular proliferation with Masson‐like features | Veno‐capillary malformation |
| PIK3CA; GNA11 | c.3140A > G (p.His1047Arg); c.627G > C (p.Gln209His) | 17; 17 | 57/m | Skin pericumbilical | Unknown | Veno‐capillary malformation |
| PIK3CA; GNA11 | c.1633G > A (p.Glu545Lys); c.627G > T (p.Gln209His) | 7; 6 | 45/m | Skin nose | Venous malformation | Veno‐capillary malformation |
| PIK3CA; IDH1 | c.3140A > G (p.His1047Arg); c.394C > T (p.Arg132Cys) | 12; 9 | 5/f | Scapula | Venolymphatic malformation, atypical by ultrasound | SCH |
| Retrospective panel | ||||||
| TEK | c.2690A > G (p.Tyr897Cys) | 3 | 11/f | Jaw | Venous malformation | Venous malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 5 | 20/f | Labia minora | Venous malformation | Venous malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 11 | 15/m | Soft tissue leg | Venous malformation | Veno‐capillary malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 9 | 67/f | Upper lip | Venous lake | Combined malformation (extensive lymphatic component) |
| TEK | c.2690A > G (p.Tyr897Cys) | 4 | 80/f | Subcutis | Unknown | Combined malformation (extensive lymphatic component) |
| TEK | c.2690A > G (p.Tyr897Cys) | 4 | 9/f | Groin | Venous malformation, also anemia. d.d. Blue rubber bleb nevus. | Combined malformation (extensive lymphatic component) |
| TEK | c.2740C > T (p.Leu914Phe) | 8 | 33/m | Lower arm | Venous malformation | Venous malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 5 | 17/f | Leg | Unknown | Veno‐capillary malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 5 | 10/m | Lip | Venous malformation | Veno‐capillary malformation |
| TEK | c.2740C > T (p.Leu914Phe) | 9 | 15/m | Soft tissue arm | Unknown | Veno‐capillary malformation |
| TEK | c.2689 T > C (p.Tyr897His) | 12 | 2/m | Arm | Localized atypical tumor by ultra sound. d.d. vascular malformation | Veno‐capillary malformation |
| GNAQ | c.548G > A (p.Arg183Gln) | 7 | 56/f | Face | Port wine stain with hypertrophy | Venous malformation |
| KRAS | c.34G > T (p.Gly12Cys) | 6 | 76/m | Lower leg | Arteriovenous malformation (AVM) with ulceration | AVM |
| KRAS | c.34G > T (p.Gly12Cys) | 6 | 68/f | Finger | AVM | AVM |
| KRAS | c.35G > T (p.Gly12Val) | 3 | 17/f | Brain | Unknown | Venous malformation |
| GNA11 | c.626A > T (p.Gln209Leu) | 9 | 45/m | Skin ear canal | Unknown | Veno‐capillary malformation |
| PIK3CA; GNAQ | c.1624G > A (p.Gln542Lys); c.627A > C (p.Gln209His) | 15; 13 | 27/m | Skin | High flow lesion, d.d. AVM | Veno‐capillary malformation |
| PIK3CA; IDH1 | c.1624G > A (p.Gln542Lys); c.394C > T (p.Arg132Cys) | 24; 20 | 21/m | Subcutis leg | Atypical vascular lesion | SCH |
Abbreviations: KTS, Klippel Trenaunay syndrome; AVM, arteriovenous malformation; SCH, spindel cell hemangioma.