Table 1. Clinical features in nine patients with GLA.

Patient	Age (y)	Sex	PIK3CA variant	LM	Effusions	Osteolysis	Visceral involvement	Associated vascular anomalies	Skin alteration	Rapamycin treatment	Rapamycin response	Other
GLA002	17	F	c.3140A>G; p.His1047Arg	Pelvic LM (predominantly microcystic) affecting lumbosacral spine and gluteal region	−	Massive (axial and appendicular) osteolysis in iliac bones, sacro-coccygeal vertebrae and vertebral body L5, causing paraplegia of lower limbs	Pelvic organs	Atypical epidermoid hemangioma in cranial vault	Sacral patch	+	Pain reduction; improvement in ability to walk	Treatment with radiotherapy and interferon; secondary ovarian dysfunction; idiopathic intracranial hypertension; hyperthyroidism; dysmetria; distal shortening of the ulna; accessory cervical rib; scoliosis; slow growth
GLA006	23	M	c.3140A>T; p.His1047Leu	LM (predominantly macrocystic) in the arm (skin, soft tissues, and humerus), covering the right axilla, shoulder, and right hemithorax (pleura, pericardium, anterior mediastinum, thymus, diaphragm, ribs and vertebrae), and spleen	Chylothorax, hemothorax, chylopericardium	Osteolysis (axial and appendicular) of the humerus, clavicle, and ribs on the right side	Spleen	−	Upper limb	−	NA	Deceased
GLA011	20	M	None	Bilateral cervico-thoracic macrocystic LM with discrete bilateral mediastinal progression (up to aorto-pulmonary window) and around the vertebral arteries in the cranial region	−	Multiple (axial and appendicular) lytic lesions predominantly affecting dorsal and lumbar vertebrae, third left rib, pelvis, both middle thirds of humerus, bilateral supraacetabular region, and proximal portions of femurs	−	−	−	+	Pain reduction; improvement of dysphagia; breathing	Multiple cervical LM infections
GLA022	6	F	None	Right mediastinal thoracic macrocystic LM with supraclavicular and external thoracic extension; two small splenic LMs	−	−	Lung, spleen	Upper cava aneurysm	−	−	NA	Diffuse supra and infratentorial cortico-subcortical atrophy; breathing difficulties; right lung diffuse alveolar damage; squamous metaplasia and tracheobronchial ulcerations; herpes simplex virus type II ulcers in tongue; chronic duodenal peptic ulcer; thymus atrophy by compression; deceased
GLA038	15	F	None	Multiple LMs: retroperitoneal infiltrating the spine, with macrocystic component, the biggest in the left hypochondrium, right flank, and right paravesical; and microcystic, most important in soft tissues of right hemipelvis	−	Multiple (axial and appendicular) bone lesions in vertebral bodies D12, L1, L3, L4, L5, sacrum, and iliac crests	Multiple focal lesions in spleen	−	−	+	Pain reduction	Complete androgen insensitivity syndrome; hypogonadotropic hypogonadism; absence of Müllerian structures and abdominal dysplastic testicle; umbilical hernia; osteopenia
GLA051	35	F	c.1624G>A; p.Glu542Lys	Retroperitoneal and right thigh mixed (macro/microcystic) LMs	Chylous ascites	−	Kidney compression; nephrectomy	−	−	+	Pain reduction	Steinert disease; secondary lymphedema in right leg; severe chronic pain in the outer area of the right knee; epigastric hernia; surgery for polyps in the gallbladder
GLA053	4	M	None	Thoracic LM (predominantly microcystic)	Chylopericardium	Osteolysis (axial) in upper and lower part of left ribs, arches 10 to 12 missing	Left lung	−	Two large hyperchromic lesions in left hemithorax	+	Pain reduction, metabolic improvement, size reduction	Severe respiratory insufficiency; cardiac tamponade; bronchospasm; thrombopenia; failure to thrive; growth delay in size and weight, gastrostomy, and Port-a-Cath
GLA054	38	F	c.1636C>A; p.Gln546Lys	LM in left upper limb and hemithorax present since birth (predominantly microcystic)	Hemothorax	−	−	−	−	+	Pain reduction	−
GLA061	16	M	c.1624G>A; p.Glu542Lys	Cervicofacial and thoracic complex LM (mixed, with slight macrocystic predominance)	−	−	−	Cervical and cranial LVM; intracraneal VM	−	+	Pain reduction	−

F, female; LVM, lymphatic venous malformation; M, male; NA, not applicable; VM, venous malformation.