Table 1 Details of genotype and phenotypic characteristics of enrolled participants.
Patient number | 01-01 | 01-02 | 02-01 | 06-01 | 02-02 | 04-01 | 09-01 | 16-01 | 01-03 |
Sex | M | F | M | F | M | F | F | F | M |
PIK3CA variant | c.1624G>A | c.1624G>A | c.3140A>G | c.1633G>A | c.311C>T | c.328_330delGAA | c.1133G>A | c.1035T>A | c.1258T>C |
p.(Glu542Lys) | p.(Glu542Lys) | p.(His1047Arg) | p.(Glu545Lys) | p.(Pro104Leu) | p.(Glu110del) | p.(Cys378Tyr) | p.(Asn345Lys) | p.(Cys420Arg) | |
General presentation | KTS | KTS | CLOVES | KTS | CLOVES | CLOVES | KTS | CLOVES | CLOVES |
Fibroadipose or soft tissue overgrowth | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Affected areas of overgrowth | Right leg | Right foot | Right calf, right foot | Left leg | Legs | Right leg, right trunk | Thighs, arms | Trunk | Lower trunk, lower limbs |
Regional lipohypoplasia (affected areas) | N | N | N | Y | Y | N | N | Y | Y |
Type of vascular Malformations | Deep and superficial lymphatic malformation (right leg and pelvis) | Pelvic vascular agenesis/malformation | Varicose veins | Lymphatic malformation (left leg); capillary malformation (4th toe); varicose veins (right buttock) | Extensive capillary malformation (trunk and extremities); varicose veins | Extensive capillary malformation (abdomen and trunk), lymphatic deep and superficial malformation (right lower limb), varicose veins (left leg) | Capillary malformations (legs, arms, trunk and lower limbs), lymphedema | N | Lymphatic deep and superficial malformation (lower trunk and lower limbs) |
Thromboembolic disease | Y | Y | N | Y | N | Y | N | N | Y |
Hemorrhage | N | Rectal bleeding | N | Vaginal bleeding | N | N | Abundant menstruations, short cycles | N | N |
Epidermal nevus | N | N | N | N | N | N | N | N | N |
Extremities | Overgrowth of right foot | Overgrowth of right toe | Overgrowth of right plantar and toe; plantar connective tissue hamartoma | Overgrowth of left foot | Overgrowth of feet | Overgrowth of right toe | Bilateral and symmetrical brachymetacarpy (4th and 5th segments) and brachymetatarsy (short toes with short and buried nails) | Enlarged feet with wide spaced toes | Y |
Spine | N | N | N | N | Kyphosis | Scoliosis | N | Scoliosis | Scoliosis |
Others | Limited leg extension | N | N | Recurrent soft tissue infections | N | Left knee algodystrophy, | Body hypertrophy, bilateral conductive deafness, leg length discrepancy, left knee pain | N | Leukocytoclastic vasculitis, glomerulonephritis, recurrent soft tissue infections |
BMI (kg/m2) | 25.2 | 25.5 | 24.3 | 31.9 | 27.7 | 25.0 | 29.7 | 23.7 | 33.6 |
OFC (cm) | ND | ND | ND | 55 | 57 | 55 | 54.5 | 54 | ND |
Development anomalies | N | N | N | N | N | Learning disabilities | N | N | N |
Procedures/surgery | Venous embolization and ethanol sclerotherapy | Toe amputation | Amputation (all left foot’s toes, 2nd and 3rd metatarsals), soft tissue reduction, and liposuction | Multiple debulking surgeries | Multiple surgeries (debulking, vascular, cutaneous, spine, venous stripping) | N | N | Right toes amputation (2nd to 4th), plantar soft tissue ablation; multiple abdominal liposuctions; urgent median laparotomy for S. aureus sepsis | N |
Overall improvement | Reduction of pain (slight), improvement: muscle and joint flexibility, better comfort when driving a car | Reduction: digestive hemorrhage (very important), pain (important), antalgic intake, correction of chronic deep anemia leading to disappearance of chronic asthenia and withdrawal of chronic blood transfusions | Reduction of: hypertrophy (-1 cm diameter on affected foot compared to baseline) pain, antalgic intake | Reduction: pain (significant), antalgic intake, asthenia, headaches, vaginal bleeding (very important) | N | Reduction: hypertrophy (−2 cm diameter on affected leg compared to baseline) | Not evaluated (early termination because of drug-related adverse event) | Slight esthetic improvement of aspect of lipoma | Reduction of left calf volume, reported better overall general state |
Pain (important), antalgic intake | |||||||||
Improvement: walking and standing durations, QoL | Improvement: walking and standing durations, QoL, social life and mood | Improvements: walking and standing durations, QoL | |||||||
Important pain reduction with diminution of antalgic intake) |
Patient number | 08-01 | 11-01 | 06-02 | 12-01 | 02-03 | 04-02 | 09-02 | 16-02 |
Sex | F | F | F | F | F | M | F | F |
PIK3CA variant | c.1258T>C | c.1093G>A | c.3140A>G | c.1624G>A | c.3062A>G | c.3129G>A | c.353G>A | c.3140A>G |
p.(Cys420Arg) | p.(Glu365Lys) | p.(His1047Arg) | p.(Glu542Lys) | p.(Tyr1021Cys) | p.(Met1043Ile) | p.(Gly118Asp) | p.(His1047Arg) | |
General presentation | KTS | KTS | KTS | KTS | KTS | KTS with facial infiltrative lipomatosis | KTS | KTS |
Fibroadipose or soft tissue overgrowth | Y | Y | N | Y | Not assessable (due to overweight) | Y | Y | N |
Affected areas of overgrowth | Right leg | Left lower limb with buried nails, left face, both hands | Left leg with bony overgrowth | Left leg, left foot | Right leg, left leg | Lower limbs, hemiface | Right lower trunk, right lower limb | Left upper limb |
Regional lipohypoplasia (affected areas) | N | N | N | N | N | N | N | N |
Type of vascular malformations | Capillary and lymphatic malformation, with skin lymphangiectasia and purple nevus flammeus from right buttock to feet | Superficial capillary malformation, arteriovenous malformation, nevus roseus, phlebectasia | Capillary keratotic lymphangiectasia | Capillary lymphatic malformation of left leg, left foot and skin lymphagectasias | Extensive superficial capillary malformation (nevus roseus) and bilateral lymphoedema (both legs) and microcystic malformation | Extensive superficial capillary malformation (nevus roseus) and bilateral lymphoedema (both legs) | Superficial capillary lymphatic malformation of right lower limb and right lower trunk, skin lymphangiectasias of lower back | Microcystic lymphatic malformation with skin lymphangiectasias |
Cutaneous hemangiomas, and varicose veins of left leg | ||||||||
Thromboembolic disease | N | N | N | Y | Y | N | N | N |
Hemorrhage | N | N | N | Menorrhagia, history of rectal bleeding | Abundant menstruation | N | N | N |
Epidermal nevus | N | N | N | N | Y | N | N | N |
Extremities | Lymphatic malformation of 3rd, 4th, and 5th right toes | Hypertrophy of left foot, both hands | N | Lymphatic malformation, soft tissue hyperplasia with debulking surgery | Macrodactyly of right middle finger, left index finger | Superficial capillary malformation (nevus roseus) and bilateral lymphedema | Capillary malformation, with sequels of debulking surgery | Muscular retraction of muscular compartments with left hand arthrogryposis |
Spine | N | N | N | N | Lordosis | N | N | N |
Others | Erysipelas | N | Chronic migraine | Subcutaneous lymphangiectasis, edema of outer lips of vagina with associated lymphatic collection | Arthrosis, hypothyroidism with goiter, left jugular vein hypoplasia, anemia, spleen hamartoma, mucosal and skin lesions/infections (fungal infection, vaginal mycosis, eczema, lichen) | N | N | Left elbow flexion deformity |
BMI (kg/m2) | 21.5 | 24.9 | 18.2 | 21.2 | 60.8 | 32.3 | 30.1 | 19.2 |
OFC (cm) | 57.5 | 57 | 54 | ND | 58 | 59.5 | ND | 53.5 |
Development anomalies | N | N | N | N | N | Behavioral disorder | N | N |
Procedures/surgery | N | Left femoral and tibial osteotomy, cervix conization | N | Left foot (2nd toe ablation, ablation of 1st and 3rd nails) | N | Bilateral carpal tunnel | Right foot debulking surgery between 2nd and 3rd toe | N |
Overall improvement* | N | Reduction of left leg volume (can wear jeans); significant pain reduction, improved physical (started jogging) and psychological condition (stopped alprazolam); disappearance of headaches | Pain reduction | Pain reduction | Reduction of leg edema and induration, muscle cramps and muscle pain, asthenia, mucosal and skin infections (no new infection with taselib); functional improvement (recovery of left knee flexion, disappearance of trigger knee), recovery of daily activity, walking range increased, mood improvement | Not evaluated because of drug-related adverse effect leading to patient’s withdrawal | Important reduction of angioma; stabilization of pre-existing varicose vein (right knee) at baseline; disappearance of pain, antalgic intake stopped walking range strongly improved improvement of mood | Disappearance of pain Improvement in quality of life; diminution of asthenia, mainly because of disappearance of night awakening due to pain |
