Sandbox:Hannan: Difference between revisions
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Fibro adipose vascular anomaly FAVA | Fibro adipose vascular anomaly FAVA | ||
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* Some of these lesions, associated with overgrowth, belong to the PIK3CA related overgrowth spectrum PROS | |||
==Classification== | ==Classification== |
Revision as of 18:07, 8 October 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]
Overview
Vascular Anomalies | ||||
---|---|---|---|---|
Vascular Tumors | Vascular Malformations | |||
Benign
Locally aggressive or Borderline Malignant |
Simple | Combined* | of major named vessels | associated with other anomalies |
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 |
See details | See list |
* Defined as two or more vascular malformations found in one lesion
** High flow lesions
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.
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 |
* Some of these lesions, associated with overgrowth, belong to the PIK3CA related overgrowth spectrum PROS
Classification
Classification of Vascular Malformations
Vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Simple | Combined | of major named vessels | asscoiated with other anomalies | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Combined vascular malformations*
| Anomalies of major named vessels (also known as "channel type" or "truncal" vascular malformations) | Vascular malformations associated with other anomalies
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Capillary malformations | Lymphatic malformations | Venous malformations | Arteriovenous malformations | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tables
Anomalies of major named vessels
(also known as "channel type" or "truncal" vascular malformations) |
---|
Affect
lymphatics veins arteries Anomalies of origin course number length diameter (aplasia, hypoplasia, stenosis, ectasia / aneurysm) valves communication (AVF) persistence (of embryonal vessel) |
Combined vascular malformations* | ||
---|---|---|
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 | CLAVM |
CM + VM + AVM | capillary-venous-arteriovenous malformation | CVAVM |
CM + LM + VM + AVM | capillary-lymphatic-venous-arteriovenous m. | CLVAVM |
Vascular malformations associated with other anomalies | ||
---|---|---|
Klippel-Trenaunay syndrome * | CM + VM +/-LM + limb overgrowth | |
Parkes 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 | |
Limb CM + congenital non-progressive limb overgrowth | ||
Maffucci syndrome | VM +/-spindle-cell hemangioma + enchondroma | |
Macrocephaly-CM (M-CM / MCAP) * | ||
Microcephaly-CM (MICCAP) | ||
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 |
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.[1]
- Etiology and pathophysiology are not clearly defined but majority of the lesions are congenital while a one fifth may be associated with trauma.[2]
- 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.[2][1][3]
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).[4][5]
- 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.[4][6][7]
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.[8]
- 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.[8][9]
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.[10]
- 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.[11]
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.[12]
- 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.[12]
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.[13][14]
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.[15][16]
- Etiology and pathogenesis have not been established yet. Some suggestions include PIK3CA mutations, polygenic inheritance, VG5Q mutation and obstruction of the venous system.[15][17]
- Diagnosis can be made on clinical manifestations and can be confirmed by Doppler ultrasound and magnetic resonance angiography. Management depends on clinical manifestations.[15][17]
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.[18]
- 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.[18]
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.[19]
- Patients should be evaluated to check for malignant transformation. Some recommend CT scans and PET scans at regular intervals.[20]
- 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.[21]
- 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.[22][23]
- 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.[22]
- 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.[22][24]
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.[25][26][27][28]
- 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.[28]
- 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.[25][29]
- 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.[30][31]
- 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.[30]
- 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.[30][32]
- 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.[33][34]