Vascular anomalies

Vascular Anomalies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2], Anmol Pitliya, M.B.B.S. M.D.[3]

Overview

Vascular anomalies constitute a wide array of disorders ranging from benign lesions such as infantile hemangioma to aggressive malignant tumors such as angiosarcoma. Commonly used misnomers and confusing nomenclature has often presented difficulties for accurate diagnosis and appropriate management. International Society for the Study of Vascular Anomalies (ISSVA) has now classified vascular anomalies into vascular tumors and vascular malformations with an unclassified category for lesions that show clinical and histological characteristics unique from disorders classified in vascular tumors and vascular malformations.

Classification

Vascular Anomalies
Vascular Tumors	Vascular Malformations
	Simple vascular malformation	Combined vascular malformation*	Vascular malformation of major named vessels	Vascular malformation associated with other anomalies
Benign Locally aggressive or Borderline Malignant	Capillary malformations Lymphatic malformations Venous malformations Arteriovenous malformations** Arteriovenous fistula**	Capillary venous malformation Capillary lymphatic malformation Lymphatic venous malformation Capillary lymphatic venous malformation Capillary arteriovenous malformation Capillary lymphatic arteriovenous malformation Others For details, Click here	For details, Click here	For details, Click here
* Defined as two or more vascular malformations found in one lesion ** High flow lesions

Classification of Vascular Tumors

Vascular tumors

Benign

Locally aggressive or borderline

Malignant

Infantile hemangioma / Hemangioma of infancy

Kaposiform hemangioendothelioma*

Angiosarcoma

Congenital hemangioma*

Retiform hemangioendothelioma

Epithelioid hemangioendothelioma

Tufted angioma*

Papillary intralymphatic angioendothelioma (PILA), Dabska tumor

Others

Spindle-cell hemangioma

Composite hemangioendothelioma

Epithelioid hemangioma

Pseudomyogenic hemangioendothelioma

Pyogenic granuloma (also known as lobular capillary hemangioma)

Polymorphous hemangioendothelioma

Others • Microvenular hemangioma • Anastomosing hemangioma • Glomeruloid hemangioma • Papillary hemangioma • Intravascular papillary endothelial hyperplasia • Cutaneous epithelioid angiomatous nodule • Acquired elastotic hemangioma • Littoral cell hemangioma of the spleen

Hemangioendothelioma not otherwise specified

' Related lesions • Eccrine angiomatous hamartoma • Reactive angioendotheliomatosis • Bacillary angiomatosis

Kaposi sarcoma

Others

^*congenital hemangioma (rapidly involuting type) and tufted angioma may be associated with thrombocytopenia and/or consumptive coagulopathy in some cases. Many experts consider tufted angioma and kaposiform hemangioendothelioma to be part of a spectrum rather than distinct entities

Classification of Vascular Malformations

Vascular malformations

Simple vascular malformations

Combined vascular malformations

Vascular malformations of major named vessels

Vascular malformations asscoiated with other anomalies

* CM + VM Capillary-venous malformation CVM CM + LM Capillary-lymphatic malformation CLM CM + AVM Capillary-arteriovenous malformation CAVM LM + VM Lymphatic-venous malformation LVM CM + LM + VM Capillary-lymphatic-venous malformation CLVM CM + LM + AVM Capillary-lymphatic-arteriovenous malformation CLVM CM + VM + AVM Capillary-venous-arteriovenous malformation CVAVM CM + LM + VM + AVM Capillary-lymphatic-venous-arteriovenous malformation CLVAVM

(also known as "channel type" or "truncal" vascular malformations) Affect • Lymphatics • Veins • Arteries Anomalies of • Origin • Course • Number • Diameter (aplasia, hypoplasia, stenosis, ectasia / aneurysm) • Valves • Communication (AVF) • Persistence (of embryonal vessel)

Klippel-Trenaunay syndrome CM + VM +/-LM + limb overgrowth Parke's Weber syndrome CM + AVF + limb overgrowth Servelle-Martorell syndrome Limb VM + bone undergrowth Sturge-Weber syndrome Facial + leptomeningeal CM + eye anomalies +/-bone and/or soft tissue overgrowth Maffucci syndrome VM +/-spindle-cell hemangioma + enchondroma CLOVES syndrome LM + VM + CM +/-AVM+ lipomatous overgrowth Proteus syndrome CM, VM and/or LM + asymmetrical somatic overgrowth Bannayan-Riley-Ruvalcaba sd lower lip CM + face and neck LM + asymmetry and partial/generalized overgrowth Limb CM + congenital non-progressive limb overgrowth Macrocephaly-CM (M-CM / MCAP) Microcephaly-CM (MICCAP)

Capillary malformations (CM)

Lymphatic malformations (LM)

Venous malformations (VM)

Arteriovenous malformation(AVM)

Arteriovenous fistula

Nevus simplex / salmon patch, “angel kiss”, “stork bite”

Common (cystic) LM • Macrocystic LM • Microcystic LM • Mixed cystic LM

Common VM

Sporadic

Sporadic

Cutaneous and/or mucosal CM (also known as “port-wine” stain) • Nonsyndromic CM • CM with CNS and/or ocular anomalies (Sturge-Weber syndrome) • CM with bone and/or soft tissues overgrowth • Diffuse CM with overgrowth (DCMO)

Generalized lymphatic anomaly (GLA) Kaposiform lymphangiomatosis (KLA)

Familial VM cutaneo-mucosal (VMCM)

In HHT

In HHT

Reticulate CM • CM of MIC-CAP (microcephaly-capillary malformation) • CM of MCAP (megalencephaly-capillary malformation-polymicrogyria)

LM in Gorham-Stout disease

Blue rubber bleb nevus (Bean) syndrome VM

In CM-AVM

In CM-AVM

CM of CM-AVM

Channel type LM

Glomuvenous malformation (GVM)

Others

Others

Cutis marmorata telangiectatica congenita (CMTC)

“Acquired” progressive lymphatic anomaly (so called acquired progressive "lymphangioma")

Cerebral cavernous malformation (CCM)

Others

Primary lymphedema

Familial intraosseous vascular malformation (VMOS)

Telangiectasia • Hereditary hemorrhagic telangiectasia (HHT) • Others

Others

Verrucous venous malformation (formerly verrucous hemangioma)

Others

Provisionally unclassified vascular anomalies

Provisionally unclassified vascular anomalies
Intramuscular hemangioma *
Angiokeratoma
Sinusoidal hemangioma
Acral arteriovenous "tumour"
Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral angiomatosis with thrombocytopenia (MLT/CAT)
PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue (PHOST)
Fibro adipose vascular anomaly (FAVA)

* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM. Some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy.

Genetics in Vascular Anomalies

Causal genes of vascular anomalies
ACVRL1	Telangiectasia, AVM and AVF of HHT2
AKT1	Proteus syndrome
BRAF	Pyogenic granuloma PG
CAMTA1	Epithelioid hemangioendothelioma EHE
CCBE1	Primary generalized lymphatic anomaly (Hennekam lymphangiectasia-lymphedema syndrome)
ELMO2	Familial intraosseous vascular malformation VMOS
ENG	Telangiectasia, AVM and AVF of HHT1
EPHB4	CM-AVM2
FLT4	Nonne-Milroy syndrome (gene also named VEGFR3)
FOS	Epithelioid hemangioma EH
FOSB	Pseudomyogenic hemangioendothelioma
FOXC2	Lymphedema-distichiasis
GATA2	Primary lymphedema with myelodysplasia
GJC2	Primary hereditary lymphedema
Glomulin	Glomuvenous malformation
GNA11	Congenital hemangioma CH CM with bone and/or soft tissue hyperplasia Diffuse CM with overgrowth DCMO
GNA14	Tufted angioma TA Pyogenic granuloma PG Kaposiform hemangioendothelioma KHE
GNAQ	Congenital hemangioma CH CM "Port-wine" stain, nonsyndromic CM CM of Sturge-Weber syndrome
IDH1	Maffucci syndrome Spindle-cell hemangioma
IDH2	Maffucci syndrome Spindle-cell hemangioma
KIF11	Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome
KRIT1	Cerebral cavernous malformation CCM1
Malcavernin	Cerebral cavernous malformation CCM2
MAP2K1	Arteriovenous malformation AVM (sporadic)
MAP2K1	Ateriovenous fistula AVF (sporadic)
MAP3K3	Verrucous venous malformation (somatic)
MYC	Post radiation angiosarcoma
NPM11	Maffucci syndrome
PDCD10	Cerebral cavernous malformation CCM3
PIK3CA	Common (cystic) LM (somatic)* Common VM (somatic)* Klippel-Trenaunay syndrome* Megalencephaly-capillary malformation-polymicrogyria (MCAP)* CLOVES syndrome* CLAPO syndrome* Fibro adipose vascular anomaly FAVA
PTEN	Bannayan-Riley-Ruvalcaba syndrome PTEN (type) Hamartoma of soft tissue / "angiomatosis" of soft tissue
PTPN14	Lymphedema-choanal atresia
RASA1	CM-AVM1 Parkes Weber syndrome
SMAD4	Telangiectasia, AVM and AVF of Juvenile polyposis hemorrhagic telangiectasia JPHT
SOX18	Hypotrichosis-lymphedema-telangiectasia
STAMBP	Microcephaly-CM (MIC-CAP)
TEK (TIE2)	Common VM (somatic) Familial VM cutaneo-mucosal VMCM Blue rubber bleb nevus (Bean) syndrome (somatic)
TFE3	Epithelioid hemangioendothelioma EHE
VEGFC	Primary hereditary lymphedema
VEGFR3	Nonne-Milroy syndrome (gene also named FLT4)

*Some of these lesions, associated with overgrowth, belong to the PIK3CA related overgrowth spectrum PROS

Provisionally unclassified vascular anomalies

Intramuscular hemangioma

• Characterized by benign proliferation of vascular channels. Majority of lesions occur in subcutaneous adipose tissues, followed by muscles. Thigh and calf are most common sites of occurrence. Majority of the lesions are asymptomatic. Typical clinical presentation includes chronic pain and swelling that both may increase with exercise of affected muscle due to increased blood flow. Other clinical manifestations may include pulsations, discoloration over the lesion, lesion enlargement when in dependent position, increased temperature, muscle contracture, tenderness, and muscle weakness and fatigue.
• Intramuscular hemangiomas may be associated with Kasabach-Merritt syndrome characterized by thrombocytopenia and/or consumptive coagulopathy. This lesion may also lead to functional impairment, congestive cardiac failure due to arteriovenous shunting, pressure symptoms, skin necrosis and may also erode bone.
• Etiology and pathophysiology are not clearly defined but majority of the lesions are congenital while a one fifth may be associated with trauma.
• MRI is the diagnostic study of choice although X-RAY and ultrasound may be used as initial studies. Treatment is generally not indicated for asymptomatic lesions. Management options for symptomatic, complicated lesions and for cosmetic reasons may include laser ablation, systemic corticosteroids, cryotherapy, embolization, radiation, compression sclerotherapy, and surgical excision although surgical excision is usually treatment of choice in majority of the cases.

Angiokeratoma

• A muco-cutaneous vascular lesion with wart-like papular appearance characterized by dilated capillaries in the dermis and hyperkeratotis of the overlying epidermis. Clinically it may manifest as solitary or multiple hyperkeratotic papules that may be localized or generalized, most typically on scrotum, thighs, lower extremity, abdomen, trunk, tongue, penis and labia majora. Majority of the lesions are asymptomatic but some may ulcerate and/or bleed.
• It may be classified into following entities:
  • Fordyce’s angiokeratoma (arising on the genitals)
  • Mibelli’s angiokeratoma (dorsum of toes and fingers)
  • Angiokeratoma circumscriptum naeviforme (unilateral large keratotic plaques)
  • Angiokeratoma corporis diffusum (ACD) (generalized lesions between umbilicus and the knee)
• Angiokeratomas are more prevalent among males as compared to females. Increased venous pressure and radiation therapy have been cited as possible causes. Angiokeratomas have been associated with enzyme deficiencies such as alpha-galactosidase A (Fabry disease), α-fucosidase (fucosidosis), neuraminidase (sialodosis), aspartyl glycosaminase (aspartyl glucosaminuria), β-mannosidase (β- mannosidosis), α-N-acetyl galactosaminidase (Kansaki disease), and β-galactosidase (adult onset GM1 gangliosidosis).
• The diagnosis is mainly clinical but biopsy may be required. Associated enzyme deficiencies and systemic disorders must be ruled out. Treatment is generally not indicated but if so required then excision, electrocautery, cryotherapy, or laser ablations are the options.

Sinusoidal hemangioma

• A variant of cavernous hemangioma characterized histopathologically by presence of dilated thin-walled vascular channels, that vary in size, exhibiting nodular proliferation with sinusoidal arrangement. Pseudopapillary structures may also be present. Clinically majority of the lesions manifest in female adults as single, well-defined, painless, subcutaneous nodule with bluish color. Most frequent locations are trunk, extremities and breasts. Painless swelling is the most common patient complaint.
• Abnormalities of vasculogenesis and angiogenesis have been proposed as possible pathogenesis but it is not well-established.
• Combination of clinical manifestations and histopathological features is used for diagnosis. Surgery (wide excision of tumor) is the treatment of choice if treatment is required.

Acral arteriovenous "tumour"

• Congenital or acquired lesion manifesting clinically as asymptomatic mass or may present with pulsatile swelling, headache, localized throbbing pain, tinnitus and bleeding. Histopathologically they are characterized by arterio-venous connection without connecting capillary with or without intracranial component. The lesion derived its name from its acral distribution.
• Etiology can be classified as following: Congenital, traumatic, infectious and inflammatory and familial.
• Although diagnosis can be made clinically, angiography is the gold standard diagnostic modality to diagnose and define the extent of the lesion. Management regimen may include surgical excision, ligation of the supplying arteries, embolization, and intralesional sclerosing injection.

Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral angiomatosis with thrombocytopenia (MLT/CAT)

• Rare congenital disorder characterized by proliferation of vascular channels in multiple organs associated with thrombocytopenia of variable degree. Lesions may manifest themselves on skin, gastrointestinal tract, lungs, brain, bone, liver, spleen and muscles. Majority of cutaneous lesions present as multiple red to blue papules, plaques, nodules on trunk and extremities. Gastrointestinal bleeding due to multiple hemorrhagic lesions is the cause of mortality in majority of the patients. Similar lesions in brain and lungs may cause severe cerebral edema and pulmonary hemorrhage.
• Disease may manifest without cutaneous involvement or thrombocytopenia. Biopsy typically reveals proliferation of well differentiated vascular channels with intravascular papillary structure and thrombi, sometimes with hobnail appearance of lining endothelial cells.
• Biopsy followed by histopathological and immunohistochemical are required for diagnosis. Management is not well-established and disorder has a poor prognosis with high mortality. Recently sirolimus and bevacizumab have been used to treat this diorder with some success.

Fibro adipose vascular anomaly (FAVA)

• Vascular disorder typically manifesting as infiltration of muscles by fibrofatty tissues, atypical venodilation associated with localized pain, and contracture of the affected muscles. Majority of the lesions involve calf muscles and may present as painful mass, contracture of the extremity, and decreased dorsiflexion at ankle joint. Skin is not typically involved. Histological studies demonstrates fibrous and adipose tissue and congregations of venous channels with abnormal lymphatic component.
• Somatic activating mutations in PIK3CA that encodes phosphatidylinositol 3-kinase (PI3K), an enzyme functioning in cell growth, proliferation, differentiation, and survival.
• Clinical and radiological findings are often sufficient to form the diagnosis. Inconclusive cases my require biopsy. Surgical resection is the often the preferred treatment and is more effective than sclerotherapy, the alternative therapy.

Vascular malformations associated with other anomalies

Klippel-Trenaunay syndrome

• First described by Klippel and Trenaunay in 1900, this congeital syndrome is characterized by presence of capillary malformations, venous malformations, and soft tissues and bone hypertrophy. Lymphatic malformations may or may not be present. Capillary malformations typically present in form of capillary hemangioma and can occur anywhere on the body while venous and lymphatic malformations, and soft tissue and bone hypertrophy usually involves the extremities.
• Clinical manifestations are unilateral in 85% of the cases and may include localized pain and discomfort, leg length discrepancy due to hemihypertrophy, developmental delay, limb abnormalities such as polydactyly, macrodactyly, syndactyly, thrombophlebitis, osteomyelitis, pathological fractures, heart failure, erysipelas, venous thrombosis due to malformations, pulmonary embolism, gastrointestinal bleeding due to venous overload in the internal iliac vein and ophthalmic abnormalities such as telangiectasia, orbital varix, strabismus, oculosympathetic palsy, Marcus-Gunn pupil, iris coloboma and heterochromia, cataracts, persistent fetal vasculature and varicosities.
• Etiology and pathogenesis have not been established yet. Some suggestions include PIK3CA mutations, polygenic inheritance, VG5Q mutation and obstruction of the venous system.
• Diagnosis can be made on clinical manifestations and can be confirmed by Doppler ultrasound and magnetic resonance angiography. Management depends on clinical manifestations.

Parkes Weber syndrome

• Characterized by a cutaneous flush with underlying multiple micro-AVFs (arteriovenous fistulas), in association with soft tissue and skeletal hypertrophy of the affected limb. Clinical Presentation enlarged arteries and veins, capillary or venous malformations, cutaneous blush, arteriovenous fistulas, and enlargement of limb.
• Mutation in the RASA1 gene has been found to be associated with this syndrome.
• To learn more about Parkes Weber syndrome, click here.

Servelle-Martorell syndrome

• Also called phlebectatic osteohypoplastic angiodysplasia, this rare syndrome is characterized by venous malformations such as abnormal location of vein, partial or complete absence of valves, and/or venous hypoplasia or aplasia and undergrowth of bone. These abnormalities may also be associated with limb hypertrophy and arterial malformations.
• Clinical manifestations may include cutaneous compressible lesions due to malformations, cellulitis, lesion limb shortening, joint and soft tissue pain and swelling, tortuous limbs, reduced muscle mass, venous thrombosis, consumption coagulopathy, pathological fractures and bone tenderness.
• Combination of clinical and radiological findings is used to form the diagnosis, MRI can assess the involvement and extent of lesions. Treatment is mainly conservative with surgery being used in some cases to excise and/or correct malformations.

Sturge-Weber syndrome

• Congenital syndrome characterized by capillary malformations involving face and laptomeninges and eye abnormalities. There may also be bone and/or overgrowth.
• Clinical manifestations may include seizures, port-wine stain on the forehead and upper eyelid of one side of the face, muscle weakness, developmental delays and mental retardation, glaucoma, and buphthalmos.
• Associated with mutations in GNAQ gene that encodes for members of G protein family.
• To learn more about Sturge-Weber syndrome, click here.

Maffucci syndrome

• A rare disorder characterized by presence of venous malformations associated with multiple enchondromas, benign cartilage-forming tumors, and multiple soft tissue hemangiomas and lymphangiomas. These benign tumors have tendency to undergo malignant transformation in maffuci syndrome. People with maffuci syndrome are also at increased risk of developing other malignant tumors such as glioma, glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinomas, hepatocellular carcinoma, pancreatic, and breast malignancies. Clinical manifestations depend on the coexisting lesions.
• Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2), enzymes involved in metabolism of isocitrate and α-ketoglutarate, and TP53, a cell-cycle regulator, have been found in tumors in maffuci syndrome.
• Patients should be evaluated to check for malignant transformation. Some recommend CT scans and PET scans at regular intervals.
• To learn more about maffuci syndrome, click here.

CLOVES syndrome

• CLOVES is an acronym for congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal and spinal anomalies. Vascular malformations in this syndrome include venous, capillary and lymphatic malformations with or without combined arteriovenous malformations. Pulmonary thromboembolism and respiratory failure are the cause of mortality in majority of the patients. Lipomatous and vascular abnormalities are often segmental and asymmetric in distribution and present typically on chest and abdominal wall.
• Clinical and imaging findings may include swellings due to lipomatous growths, skin discoloration, port wine stain, bilateral epidermal nevi,leg length discrepancy, developmental limb anomalies such as increased gap between the first and second toes, hemorrhage, seizures, ascites, pleural effusions, hypotension, bilateral multicystic venous and lymphatic malformations, chest wall venous dilatation, multiple congenital hemangiomas, asymmetric septal hypertrophy, renal hypoplasia, dislocated knees, scoliosis, and neural tube defect.
• Activating mutations in PICK3CA gene that encodes part of PI3K has been thought to be associated with this syndrome. These mutations may help enable the cells to grow independent of growth factors.
• This syndrome can be detected prenatally and its manifestations have been identified on prenatal ultrasound and fetal MRI. Treatment options include supportive management, surgical debulking and scletherapy but treatment is often complicated by severity of the disease resulting in anemia, coagulopathy and poor wound healing.

Proteus syndrome

• Congenital syndrome characterized by asymmetric overgrowth of multiple tissues in limbs, hamartomas and vascular lesions such as capillary malformations, venous malformations, lymphatic malformations. Cerebriform connective tissue nevi, a pathognomonic lesion if present alone, are helpful in diagnosing Proteus syndrome. It may affect multiple organs such as eyes, spleen, liver, thymus, intestine, and lungs, and may cause facial dysmorphia. Some benign and malignant neoplasms such as testicular papillary adenocarcinoma and mesothelioma.
• Clinical manifestations and findings may include hemihypertrophy, asymmetry of the limbs, scoliosis, subcutaneous tumors, soft tissues tumors such as lipoma, limb abnormalities such as macrodactyly, hyperpigmented lesions on skin, verrucous epidermal nevi, lung diseases, pulmonary embolism, venous thrombosis, glaucoma, strabismus, nystagmus, pseudopapileudema, cardiac defects such as ARVC, healed myocardial infarctions, cardiomyopathies, cardiac lipomas, and central nervous system findings. These findings may be detected prenatally or at birth but majority of the patients present after 6 months of birth.
• Somatic mutations in AKT1 gene that encodes proteins functioning in AKT/PI3K signaling pathway has been proposed to be the cause of this syndrome. This pathway functions in cell growth, differentiation and survival.
• Diagnosis is based on clinical and radiological findings and must meet general and specific criteria. Management consists of clinical and psychological assistance. This may include orthopedic consultation to stop or delay bone growth, physical rehabilitation, surgical correction of deformities such as scoliosis, dermatology consultation fro skin lesions, workup and followup for vein thrombosis and pulmonary embolism, intervention for developmental delay, and evaluation for associated neoplasms at regular intervals.
• To learn more, click here.

Bannayan-Riley-Ruvalcaba syndrome

• An overgrowth syndrome characterized by vascular malformations, macrocephaly, multiple benign neoplasm and pigmented lesions on the skin. Speckled pigmented macules on genitalia are one of the most significant diagnostic characteristics. People with this syndrome may have increased risk of developing neoplasms in many organs such as thyroid, breasts, and female genital tract although it has not been confirmed.
• Typical manifestations and findings may include multiple lipomas, hemangiomas, intestinal hamartomatous polyposis, vascular malformations such as arteriovenous malformations and capillary malformations, developmental delay, macrocephaly (>97 percentile), penile pigmented macules, thyroid abnormalities such as multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer and Hashimoto’s thyroiditis, high-arched palate, protuberant frontal bone, hypertelorism, strabismus, macrosomia, hypotonia, joint hyperextensibility, hypoglycemia, convulsions, café-au-lait spots, prominent forehead, malar hypoplasia and micrognathia.
• Mutations in PTEN gene have been thought to be the cause. This gene encodes an enzyme that acts as tumor suppressor by stopping cell division and inducing apoptosis. Both autosomal-dominant transmission and sporadic occurrence have been reported.
• Diagnosis is based on clinical findings, the most important of these findings being penile pigmented maculae, hamartomatous intestinal polyposis and macrocephaly. Management consists of psycho-social counseling and treatment of manifestations such as surgical and dermatological interventions, spinal stimulation for intractable gastrointestinal pain and screening for [[[malignancies]] associated with PTEN mutations such as annual thyroid ultrasound and mammography.
• To learn more, click here.

CLAPO syndrome

• CLAPO syndrome, a syndrome that has been diagnosed in 6 patients) is acronym for capillary malformation of the lower lip, lymphatic malformations of the face and neck, asymmetry, and partial or generalized overgrowth. Manifestations may include cutaneous lesions on head and neck and asymmetrical overgrowth.
• Somatic activating PIK3CA mutations have been found in patients with CLAPO syndrome. This gene encodes proteins that function in cell-signaling pathways.

See also

• Vascular disease
• Vascular anomaly