Latest revision as of 19:25, 26 October 2018

For information on vascular anomalies, click here

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 malformation is a blood vessel abnormality. There are many types, but the most common is arteriovenous malformation. Clinical behavior and growth cycles vary widely and it may cause clinical and aesthetic problems. International Society for the Study of Vascular Anomalies (ISSVA) has classified vascular malformation into simple malformation, combined malformation, those of major named vessels, and those associated with other anomalies. Simple malformation have been divided further into capillary malformation, venous malformation and lymphatic malformation.

Classification

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 syndrome	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

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

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

CM of CM-AVM

Channel type LM

Glomuvenous malformation (GVM)

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

Abbreviations: CM:capillary malformation; VM:venous malformation; CVM:capillary venous malformation; LM:lymphatic malformation; CLM:capillary lymphatic malformation; AVM:arteriovenous malformation; CAVM:capillary arteriovenous malformation; LVM:lymphatic venous malformation; CLVM:capillary lymphatic venous malformation; CVAVM:capillary venous arteriovenous malformation; CLVAVM:capillary lymphatic venous arteriovenous malformation; AVF:arteriovenous fistula; CLOVES:congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal/scoliosis and spinal abnormalities; M-CM:macrocephaly-capillary malformation; MCAP:megalencephaly-capillary malformation-polymicrogyria; MICCAP:microcephaly-capillary malformation; CNS:central nervous system; DCMO:diffuse capillary malformation with overgrowth; CM-AVM:capillary malformation-arteriovenous malformation; CMTC:cutis marmorata telangiectatica congenita; HHT:hereditary hemorrhagic telangiectasia; GLA:generalized lymphatic anomaly; KLA:kaposiform lymphangiomatosis; VMCM:venous malformation cutaneo mucosal; GVM:glomuvenous malformation; CCM:cerebral cavernous malformation.

Adapted from International Society for the Study of Vascular Anomalies^[1]

Simple Vascular Malformations

	Vascular Malformation
Home
Overview
Classification Simple Vascular Malformations Capillary Malformation Lymphatic Malformation Venous Malformation Arteriovenous Malformation Arteriovenous Fistula Combined Vascular Malformations Vascular Malformations of Major Named Vessels Vascular Malformations associated With other Anomalies

	Vascular malformation
	Classification and external resources
MeSH	D054079

Simple Vascular Malformations are divided into:

Capillary malformation
Lymphatic malformation
Venous malformation
Arteriovenous malformation
Arteriovenous fistula

Combined Vascular Malformations

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
Adapted from International Society for the Study of Vascular Anomalies^[1]

Abbreviations: CM:capillary malformation; VM:venous malformation; CVM:capillary venous malformation; LM:lymphatic malformation; CLM:capillary lymphatic malformation; AVM:arteriovenous malformation; CAVM:capillary arteriovenous malformation; LVM:lymphatic venous malformation; CLVM:capillary lymphatic venous malformation; CVAVM:capillary venous arteriovenous malformation; CLVAVM:capillary lymphatic venous arteriovenous malformation.

Vascular Malformations of Major Named Vessels


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)
Adapted from International Society for the Study of Vascular Anomalies^[1]

Abbreviations: AVF:arteriovenous fistula.

Vascular Malformations associated With other Anomalies

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 syndrome	lower lip CM + face and neck LM + asymmetry and partial/generalized overgrowth
Adapted from International Society for the Study of Vascular Anomalies^[1]

Abbreviations: CM:capillary malformation; VM:venous malformation; LM:lymphatic malformation; AVM:arteriovenous malformation; AVF:arteriovenous fistula; CLOVES:congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal/scoliosis and spinal abnormalities; M-CM:macrocephaly-capillary malformation; MCAP:megalencephaly-capillary malformation-polymicrogyria; MICCAP:microcephaly-capillary malformation.

Klippel-Trenaunay syndrome

First described by Klippel and Trenaunay in 1900, this congenital 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.^[2]^[3]^[4]^[5]^[6]
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.^[5]^[6]^[4]^[7]
Etiology and pathogenesis have not been established yet. Some suggestions include PIK3CA mutations, polygenic inheritance, VG5Q mutation and obstruction of the venous system.^[2]^[5]^[7]
Diagnosis can be made on clinical manifestations and can be confirmed by Doppler ultrasound and magnetic resonance angiography. Management depends on clinical manifestations.^[5]^[7]^[4]^[5]

For more information on Klippel-Trenaunay syndrome, click here

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.

For more information on 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.^[8]
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.^[8]
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.^[8]^[9]

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.

For more information on 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 Maffucci syndrome. People with Maffucci 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.^[10]^[11]^[12]
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 Maffucci syndrome.^[13]^[14]
Patients should be evaluated to check for malignant transformation. Some recommend CT scans and PET scans at regular intervals.^[12]^[11]^[15]^[12]

For more information on Maffucci 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.^[16]^[17]^[18]^[19]
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.^[16]^[19]^[18]
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.^[16]^[17]^[20]
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.^[16]^[17]

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.^[21]^[22]^[23]
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.^[21]^[22]^[23]^[24]
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.^[23]^[25]
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.^[21]^[26]

For more information about Proteus syndrome, 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.^[27]^[28]^[29]
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.^[27]^[28]^[29]
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.^[27]
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.^[27]^[29]

For more information on Bannayan-Riley-Ruvalcaba syndrome, click here.

CLAPO syndrome

CLAPO syndrome, a syndrome diagnosed in 6 patients, is an 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.^[30]^[31]
Somatic activating PIK3CA mutations have been found in patients with CLAPO syndrome. This gene encodes proteins that function in cell-signaling pathways.^[30]^[31]

References

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↑ Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV (November 2011). "Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome". Nat. Genet. 43 (12): 1256–61. doi:10.1038/ng.1004. PMC 3427908. PMID 22057234.
↑ Al-Katib S, Al-Faham Z, Grant P, Palka JC (June 2015). "The Appearance of Maffucci Syndrome on 18F-FDG PET/CT". J Nucl Med Technol. 43 (2): 131–2. doi:10.2967/jnmt.114.146480. PMID 25537758.
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↑ ^17.0 ^17.1 ^17.2 Sarici D, Akin MA, Kurtoglu S, Tubas F, Sarici SU (2014). "A Neonate with CLOVES Syndrome". Case Rep Pediatr. 2014: 845074. doi:10.1155/2014/845074. PMC 4221976. PMID 25400966.
↑ ^18.0 ^18.1 Alomari AI, Burrows PE, Lee EY, Hedequist DJ, Mulliken JB, Fishman SJ (August 2010). "CLOVES syndrome with thoracic and central phlebectasia: increased risk of pulmonary embolism". J. Thorac. Cardiovasc. Surg. 140 (2): 459–63. doi:10.1016/j.jtcvs.2010.04.023. PMID 20537357.
↑ ^19.0 ^19.1 Gopal B, Keshava SN, Selvaraj D (2015). "A rare newly described overgrowth syndrome with vascular malformations-Cloves syndrome". Indian J Radiol Imaging. 25 (1): 71–3. doi:10.4103/0971-3026.150166. PMC 4329693. PMID 25709171.
↑ Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML (June 2012). "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome". Am. J. Hum. Genet. 90 (6): 1108–15. doi:10.1016/j.ajhg.2012.05.006. PMC 3370283. PMID 22658544.
↑ ^21.0 ^21.1 ^21.2 Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
↑ ^22.0 ^22.1 El-Sobky TA, Elsayed SM, El Mikkawy DM (December 2015). "Orthopaedic manifestations of Proteus syndrome in a child with literature update". Bone Rep. 3: 104–108. doi:10.1016/j.bonr.2015.09.004. PMC 5365241. PMID 28377973.
↑ ^23.0 ^23.1 ^23.2 Hannoush H, Sachdev V, Brofferio A, Arai AE, LaRocca G, Sapp J, Sidenko S, Brenneman C, Biesecker LG, Keppler-Noreuil KM (January 2015). "Myocardial fat overgrowth in Proteus syndrome". Am. J. Med. Genet. A. 167A (1): 103–10. doi:10.1002/ajmg.a.36773. PMC 4275354. PMID 25377688.
↑ Sarman ZS, Yuksel N, Sarman H, Bayramgurler D (June 2014). "Proteus syndrome: report of a case with developmental glaucoma". Korean J Ophthalmol. 28 (3): 272–4. doi:10.3341/kjo.2014.28.3.272. PMC 4038735. PMID 24882963.
↑ Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG (December 2015). "Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome". Sci Rep. 5: 17162. doi:10.1038/srep17162. PMC 4675973. PMID 26657992.
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↑ ^27.0 ^27.1 ^27.2 ^27.3 Gontijo GM, Pinto CA, Rogatto SR, Cunha IW, Aguiar S, Alves CA (2013). "Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant--case report". An Bras Dermatol. 88 (6): 982–5. doi:10.1590/abd1806-4841.20132730. PMC 3900354. PMID 24474112.
↑ ^28.0 ^28.1 Peiretti V, Mussa A, Feyles F, Tuli G, Santanera A, Molinatto C, Ferrero GB, Corrias A (2013). "Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome". J Clin Res Pediatr Endocrinol. 5 (4): 261–5. doi:10.4274/Jcrpe.984. PMC 3890226. PMID 24379037.
↑ ^29.0 ^29.1 ^29.2 Sagi SV, Ballard DD, Marks RA, Dunn KR, Kahi CJ (January 2014). "Bannayan Ruvalcaba Riley Syndrome". ACG Case Rep J. 1 (2): 90–2. doi:10.14309/crj.2014.11. PMC 4435287. PMID 26157835.
↑ ^30.0 ^30.1 Downey C, López-Gutiérrez JC, Roé-Crespo E, Puig L, Baselga E (July 2018). "Lower lip capillary malformation associated with lymphatic malformation without overgrowth: Part of the spectrum of CLAPO syndrome". Pediatr Dermatol. 35 (4): e243–e244. doi:10.1111/pde.13514. PMID 29766551.
↑ ^31.0 ^31.1 Rodriguez-Laguna L, Ibañez K, Gordo G, Garcia-Minaur S, Santos-Simarro F, Agra N, Vallespín E, Fernández-Montaño VE, Martín-Arenas R, Del Pozo Á, González-Pecellín H, Mena R, Rueda-Arenas I, Gomez MV, Villaverde C, Bustamante A, Ayuso C, Ruiz-Perez VL, Nevado J, Lapunzina P, Lopez-Gutierrez JC, Martinez-Glez V (August 2018). "CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype". Genet. Med. 20 (8): 882–889. doi:10.1038/gim.2017.200. PMID 29446767.

[urlClassification_|_International_Society_for_the_Study_of_Vascular_Anomalies-1] 1.0 ^1.1 ^1.2 ^1.3 "Classification | International Society for the Study of Vascular Anomalies".

[pmid26451379-2] 2.0 ^2.1 Abdolrahimzadeh S, Scavella V, Felli L, Cruciani F, Contestabile MT, Recupero SM (2015). "Ophthalmic Alterations in the Sturge-Weber Syndrome, Klippel-Trenaunay Syndrome, and the Phakomatosis Pigmentovascularis: An Independent Group of Conditions?". Biomed Res Int. 2015: 786519. doi:10.1155/2015/786519. PMC 4588354. PMID 26451379.

[pmid25427442-3] Withana M, Rodrigo C, Shivanthan MC, Warnakulasooriya S, Wimalachandra M, Gooneratne L, Rajapakse S (November 2014). "Klippel-Trenaunay syndrome presenting with acanthocytosis and splenic and retroperitoneal lymphangioma: a case report". J Med Case Rep. 8: 390. doi:10.1186/1752-1947-8-390. PMC 4289367. PMID 25427442.

[pmid25293688-4] 4.0 ^4.1 ^4.2 Ricks CB, Grandhi R, Ducruet AF (October 2014). "Klippel-Trenaunay syndrome and cavernous malformations". BMJ Case Rep. 2014. doi:10.1136/bcr-2014-207486. PMC 4187537. PMID 25293688.

[pmid28458832-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 Baba A, Yamazoe S, Okuyama Y, Shimizu K, Kobashi Y, Nozawa Y, Munetomo Y, Mogami T (February 2017). "A rare presentation of Klippel-Trenaunay syndrome with bilateral lower limbs". J Surg Case Rep. 2017 (2): rjx024. doi:10.1093/jscr/rjx024. PMC 5400491. PMID 28458832.

[pmid27921060-6] 6.0 ^6.1 Tetangco EP, Arshad HM, Silva R (August 2016). "Klippel-Trenaunay Syndrome of the Rectosigmoid Colon Presenting as Severe Anemia". ACG Case Rep J. 3 (4): e161. doi:10.14309/crj.2016.134. PMC 5126491. PMID 27921060.

[pmid29930667-7] 7.0 ^7.1 ^7.2 Chagas C, Pires L, Babinski MA, Leite T (2017). "Klippel-Trenaunay and Parkes-Weber syndromes: two case reports". J Vasc Bras. 16 (4): 320–324. doi:10.1590/1677-5449.005417. PMC 5944310. PMID 29930667. Vancouver style error: initials (help)

[pmid18454870-8] 8.0 ^8.1 ^8.2 Karuppal R, Raman RV, Valsalan BP, Gopakumar T, Kumaran CM, Vasu CK (May 2008). "Servelle-Martorell syndrome with extensive upper limb involvement: a case report". J Med Case Rep. 2: 142. doi:10.1186/1752-1947-2-142. PMC 2394530. PMID 18454870. Vancouver style error: initials (help)

[pmid6284617-9] Langer M, Langer R (May 1982). "[Radiologic aspects of the congenital arteriovenous malformations, Klippel-Trenaunay type, and Servelle-Martorell type (author's transl)]". Rofo (in German). 136 (5): 577–82. doi:10.1055/s-2008-1056105. PMID 6284617.

[pmid25777744-10] McCarthy CM, Blecher H, Reich S (June 2015). "A case of myelopathy because of enchondromas from Maffucci syndrome with successful surgical treatment". Spine J. 15 (6): e15–9. doi:10.1016/j.spinee.2015.03.006. PMID 25777744.

[pmid26628708-11] 11.0 ^11.1 Tsao YP, Tsai CY, Chen WS (December 2015). "Maffucci Syndrome". J. Rheumatol. 42 (12): 2434–5. doi:10.3899/jrheum.150216. PMID 26628708.

[pmid26920730-12] 12.0 ^12.1 ^12.2 Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H (February 2016). "Maffucci syndrome and neoplasms: a case report and review of the literature". BMC Res Notes. 9: 126. doi:10.1186/s13104-016-1913-x. PMC 4769492. PMID 26920730.

[pmid24344754-13] Moriya K, Kaneko MK, Liu X, Hosaka M, Fujishima F, Sakuma J, Ogasawara S, Watanabe M, Sasahara Y, Kure S, Kato Y (March 2014). "IDH2 and TP53 mutations are correlated with gliomagenesis in a patient with Maffucci syndrome". Cancer Sci. 105 (3): 359–62. doi:10.1111/cas.12337. PMC 4317937. PMID 24344754.

[pmid22057234-14] Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV (November 2011). "Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome". Nat. Genet. 43 (12): 1256–61. doi:10.1038/ng.1004. PMC 3427908. PMID 22057234.

[pmid25537758-15] Al-Katib S, Al-Faham Z, Grant P, Palka JC (June 2015). "The Appearance of Maffucci Syndrome on 18F-FDG PET/CT". J Nucl Med Technol. 43 (2): 131–2. doi:10.2967/jnmt.114.146480. PMID 25537758.

[pmid25044986-16] 16.0 ^16.1 ^16.2 ^16.3 Emrick LT, Murphy L, Shamshirsaz AA, Ruano R, Cassady CI, Liu L, Chang F, Sutton VR, Li M, Van den Veyver IB (October 2014). "Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes". Am. J. Med. Genet. A. 164A (10): 2633–7. doi:10.1002/ajmg.a.36672. PMC 4496426. PMID 25044986.

[pmid25400966-17] 17.0 ^17.1 ^17.2 Sarici D, Akin MA, Kurtoglu S, Tubas F, Sarici SU (2014). "A Neonate with CLOVES Syndrome". Case Rep Pediatr. 2014: 845074. doi:10.1155/2014/845074. PMC 4221976. PMID 25400966.

[pmid20537357-18] 18.0 ^18.1 Alomari AI, Burrows PE, Lee EY, Hedequist DJ, Mulliken JB, Fishman SJ (August 2010). "CLOVES syndrome with thoracic and central phlebectasia: increased risk of pulmonary embolism". J. Thorac. Cardiovasc. Surg. 140 (2): 459–63. doi:10.1016/j.jtcvs.2010.04.023. PMID 20537357.

[pmid25709171-19] 19.0 ^19.1 Gopal B, Keshava SN, Selvaraj D (2015). "A rare newly described overgrowth syndrome with vascular malformations-Cloves syndrome". Indian J Radiol Imaging. 25 (1): 71–3. doi:10.4103/0971-3026.150166. PMC 4329693. PMID 25709171.

[pmid22658544-20] Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML (June 2012). "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome". Am. J. Hum. Genet. 90 (6): 1108–15. doi:10.1016/j.ajhg.2012.05.006. PMC 3370283. PMID 22658544.

[pmid29166516-21] 21.0 ^21.1 ^21.2 Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)

[pmid28377973-22] 22.0 ^22.1 El-Sobky TA, Elsayed SM, El Mikkawy DM (December 2015). "Orthopaedic manifestations of Proteus syndrome in a child with literature update". Bone Rep. 3: 104–108. doi:10.1016/j.bonr.2015.09.004. PMC 5365241. PMID 28377973.

[pmid25377688-23] 23.0 ^23.1 ^23.2 Hannoush H, Sachdev V, Brofferio A, Arai AE, LaRocca G, Sapp J, Sidenko S, Brenneman C, Biesecker LG, Keppler-Noreuil KM (January 2015). "Myocardial fat overgrowth in Proteus syndrome". Am. J. Med. Genet. A. 167A (1): 103–10. doi:10.1002/ajmg.a.36773. PMC 4275354. PMID 25377688.

[pmid24882963-24] Sarman ZS, Yuksel N, Sarman H, Bayramgurler D (June 2014). "Proteus syndrome: report of a case with developmental glaucoma". Korean J Ophthalmol. 28 (3): 272–4. doi:10.3341/kjo.2014.28.3.272. PMC 4038735. PMID 24882963.

[pmid26657992-25] Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG (December 2015). "Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome". Sci Rep. 5: 17162. doi:10.1038/srep17162. PMC 4675973. PMID 26657992.

[pmid22876373-26] Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)

[pmid24474112-27] 27.0 ^27.1 ^27.2 ^27.3 Gontijo GM, Pinto CA, Rogatto SR, Cunha IW, Aguiar S, Alves CA (2013). "Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant--case report". An Bras Dermatol. 88 (6): 982–5. doi:10.1590/abd1806-4841.20132730. PMC 3900354. PMID 24474112.

[pmid24379037-28] 28.0 ^28.1 Peiretti V, Mussa A, Feyles F, Tuli G, Santanera A, Molinatto C, Ferrero GB, Corrias A (2013). "Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome". J Clin Res Pediatr Endocrinol. 5 (4): 261–5. doi:10.4274/Jcrpe.984. PMC 3890226. PMID 24379037.

[pmid26157835-29] 29.0 ^29.1 ^29.2 Sagi SV, Ballard DD, Marks RA, Dunn KR, Kahi CJ (January 2014). "Bannayan Ruvalcaba Riley Syndrome". ACG Case Rep J. 1 (2): 90–2. doi:10.14309/crj.2014.11. PMC 4435287. PMID 26157835.

[pmid29766551-30] 30.0 ^30.1 Downey C, López-Gutiérrez JC, Roé-Crespo E, Puig L, Baselga E (July 2018). "Lower lip capillary malformation associated with lymphatic malformation without overgrowth: Part of the spectrum of CLAPO syndrome". Pediatr Dermatol. 35 (4): e243–e244. doi:10.1111/pde.13514. PMID 29766551.

[pmid29446767-31] 31.0 ^31.1 Rodriguez-Laguna L, Ibañez K, Gordo G, Garcia-Minaur S, Santos-Simarro F, Agra N, Vallespín E, Fernández-Montaño VE, Martín-Arenas R, Del Pozo Á, González-Pecellín H, Mena R, Rueda-Arenas I, Gomez MV, Villaverde C, Bustamante A, Ayuso C, Ruiz-Perez VL, Nevado J, Lapunzina P, Lopez-Gutierrez JC, Martinez-Glez V (August 2018). "CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype". Genet. Med. 20 (8): 882–889. doi:10.1038/gim.2017.200. PMID 29446767.

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@@ Line 108: / Line 108: @@
 '''Abbreviations:''' CM:capillary malformation; VM:venous malformation; CVM:capillary venous malformation; LM:lymphatic malformation; CLM:capillary lymphatic malformation; AVM:arteriovenous malformation; CAVM:capillary arteriovenous malformation; LVM:lymphatic venous malformation; CLVM:capillary lymphatic venous malformation; CVAVM:capillary venous arteriovenous malformation; CLVAVM:capillary lymphatic venous arteriovenous malformation; AVF:arteriovenous fistula; CLOVES:congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal/scoliosis and spinal abnormalities; M-CM:macrocephaly-capillary malformation; MCAP:megalencephaly-capillary malformation-polymicrogyria; MICCAP:microcephaly-capillary malformation; CNS:central nervous system; DCMO:diffuse capillary malformation with overgrowth; CM-AVM:capillary malformation-arteriovenous malformation; CMTC:cutis marmorata telangiectatica congenita; HHT:hereditary hemorrhagic telangiectasia; GLA:generalized lymphatic anomaly; KLA:kaposiform lymphangiomatosis; VMCM:venous malformation cutaneo mucosal; GVM:glomuvenous malformation; CCM:cerebral cavernous malformation.
-'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref></small>
+'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref>
 =Simple Vascular Malformations=
@@ Line 120: / Line 120: @@
 =Combined Vascular Malformations=
 {| class="wikitable"
-! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" +|Combined vascular malformations*
+! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Combined vascular malformations*
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + VM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + VM
 |capillary-venous malformation
 |CVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + LM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + LM
 |capillary-lymphatic malformation
 |CLM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + AVM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + AVM
 |capillary-arteriovenous malformation
 |CAVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|LM + VM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |LM + VM
 |lymphatic-venous malformation
 |LVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + LM + VM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + LM + VM
 |capillary-lymphatic-venous malformation
 |CLVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + LM + AVM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + LM + AVM
 |capillary-lymphatic-arteriovenous malformation
 |CLAVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + VM + AVM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + VM + AVM
 |capillary-venous-arteriovenous malformation
 |CVAVM
 |-
-|style="background:#7d7d7d; color: #FFFFFF;" align="center" +|CM + LM + VM + AVM
+| style="background:#7d7d7d; color: #FFFFFF;" align="center" + |CM + LM + VM + AVM
 |capillary-lymphatic-venous-arteriovenous m.
 |CLVAVM
 |-
-| colspan="2" style="background:#F5F5F5;" +|<small>'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref></small>
+| colspan="2" style="background:#F5F5F5;" + |<small>'''Adapted from International Society for the Study of Vascular Anomalies'''<ref name="urlClassification | International Society for the Study of Vascular Anomalies">{{cite web |url=http://www.issva.org/classification |title=Classification &#124; International Society for the Study of Vascular Anomalies |format= |work= |accessdate=}}</ref></small>
 |}
 '''Abbreviations:''' CM:capillary malformation; VM:venous malformation; CVM:capillary venous malformation; LM:lymphatic malformation; CLM:capillary lymphatic malformation; AVM:arteriovenous malformation; CAVM:capillary arteriovenous malformation; LVM:lymphatic venous malformation; CLVM:capillary lymphatic venous malformation; CVAVM:capillary venous arteriovenous malformation; CLVAVM:capillary lymphatic venous arteriovenous malformation.
@@ Line 161: / Line 161: @@
 {| class="wikitable" style="text-align:centre"
 |+
-!style="background:#4479BA; color: #FFFFFF;" align="center" + |Anomalies of major named vessels
+! style="background:#4479BA; color: #FFFFFF;" align="center" + |Anomalies of major named vessels
 (also known as "channel type" or "truncal" vascular malformations)
 |-
@@ Line 185: / Line 185: @@
 =Vascular Malformations associated With other Anomalies=
 {| class="wikitable" style="text-align:center"
-! colspan="3"  style="background:#4479BA; color: #FFFFFF;" align="center" +|Vascular malformations associated with other anomalies
+! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + |Vascular malformations associated with other anomalies
 |-
 | colspan="2" |'''[[Klippel-Trenaunay syndrome]]*'''
@@ Line 226: / Line 226: @@
 ===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]].<ref name="pmid26451379">{{cite journal |vauthors=Abdolrahimzadeh S, Scavella V, Felli L, Cruciani F, Contestabile MT, Recupero SM |title=Ophthalmic Alterations in the Sturge-Weber Syndrome, Klippel-Trenaunay Syndrome, and the Phakomatosis Pigmentovascularis: An Independent Group of Conditions? |journal=Biomed Res Int |volume=2015 |issue= |pages=786519 |date=2015 |pmid=26451379 |pmc=4588354 |doi=10.1155/2015/786519 |url=}}</ref><ref name="pmid25427442">{{cite journal |vauthors=Withana M, Rodrigo C, Shivanthan MC, Warnakulasooriya S, Wimalachandra M, Gooneratne L, Rajapakse S |title=Klippel-Trenaunay syndrome presenting with acanthocytosis and splenic and retroperitoneal lymphangioma: a case report |journal=J Med Case Rep |volume=8 |issue= |pages=390 |date=November 2014 |pmid=25427442 |pmc=4289367 |doi=10.1186/1752-1947-8-390 |url=}}</ref><ref name="pmid25293688">{{cite journal |vauthors=Ricks CB, Grandhi R, Ducruet AF |title=Klippel-Trenaunay syndrome and cavernous malformations |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=October 2014 |pmid=25293688 |pmc=4187537 |doi=10.1136/bcr-2014-207486 |url=}}</ref><ref name="pmid28458832">{{cite journal |vauthors=Baba A, Yamazoe S, Okuyama Y, Shimizu K, Kobashi Y, Nozawa Y, Munetomo Y, Mogami T |title=A rare presentation of Klippel-Trenaunay syndrome with bilateral lower limbs |journal=J Surg Case Rep |volume=2017 |issue=2 |pages=rjx024 |date=February 2017 |pmid=28458832 |pmc=5400491 |doi=10.1093/jscr/rjx024 |url=}}</ref><ref name="pmid27921060">{{cite journal |vauthors=Tetangco EP, Arshad HM, Silva R |title=Klippel-Trenaunay Syndrome of the Rectosigmoid Colon Presenting as Severe Anemia |journal=ACG Case Rep J |volume=3 |issue=4 |pages=e161 |date=August 2016 |pmid=27921060 |pmc=5126491 |doi=10.14309/crj.2016.134 |url=}}</ref>
+* First described by Klippel and Trenaunay in 1900, this [[congenital]] 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]].<ref name="pmid26451379">{{cite journal |vauthors=Abdolrahimzadeh S, Scavella V, Felli L, Cruciani F, Contestabile MT, Recupero SM |title=Ophthalmic Alterations in the Sturge-Weber Syndrome, Klippel-Trenaunay Syndrome, and the Phakomatosis Pigmentovascularis: An Independent Group of Conditions? |journal=Biomed Res Int |volume=2015 |issue= |pages=786519 |date=2015 |pmid=26451379 |pmc=4588354 |doi=10.1155/2015/786519 |url=}}</ref><ref name="pmid25427442">{{cite journal |vauthors=Withana M, Rodrigo C, Shivanthan MC, Warnakulasooriya S, Wimalachandra M, Gooneratne L, Rajapakse S |title=Klippel-Trenaunay syndrome presenting with acanthocytosis and splenic and retroperitoneal lymphangioma: a case report |journal=J Med Case Rep |volume=8 |issue= |pages=390 |date=November 2014 |pmid=25427442 |pmc=4289367 |doi=10.1186/1752-1947-8-390 |url=}}</ref><ref name="pmid25293688">{{cite journal |vauthors=Ricks CB, Grandhi R, Ducruet AF |title=Klippel-Trenaunay syndrome and cavernous malformations |journal=BMJ Case Rep |volume=2014 |issue= |pages= |date=October 2014 |pmid=25293688 |pmc=4187537 |doi=10.1136/bcr-2014-207486 |url=}}</ref><ref name="pmid28458832">{{cite journal |vauthors=Baba A, Yamazoe S, Okuyama Y, Shimizu K, Kobashi Y, Nozawa Y, Munetomo Y, Mogami T |title=A rare presentation of Klippel-Trenaunay syndrome with bilateral lower limbs |journal=J Surg Case Rep |volume=2017 |issue=2 |pages=rjx024 |date=February 2017 |pmid=28458832 |pmc=5400491 |doi=10.1093/jscr/rjx024 |url=}}</ref><ref name="pmid27921060">{{cite journal |vauthors=Tetangco EP, Arshad HM, Silva R |title=Klippel-Trenaunay Syndrome of the Rectosigmoid Colon Presenting as Severe Anemia |journal=ACG Case Rep J |volume=3 |issue=4 |pages=e161 |date=August 2016 |pmid=27921060 |pmc=5126491 |doi=10.14309/crj.2016.134 |url=}}</ref>
-* 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]].<ref name="pmid28458832" /><ref name="pmid27921060" /><ref name="pmid25293688" /><ref name="pmid29930667">{{cite journal |vauthors=Chagas CAA, Pires LAS, Babinski MA, Leite TFO |title=Klippel-Trenaunay and Parkes-Weber syndromes: two case reports |journal=J Vasc Bras |volume=16 |issue=4 |pages=320–324 |date=2017 |pmid=29930667 |pmc=5944310 |doi=10.1590/1677-5449.005417 |url=}}</ref>
+* 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|Marcus-Gunn pupil]], iris coloboma and heterochromia, [[cataracts]], persistent fetal vasculature and [[varicosities]].<ref name="pmid28458832" /><ref name="pmid27921060" /><ref name="pmid25293688" /><ref name="pmid29930667">{{cite journal |vauthors=Chagas CAA, Pires LAS, Babinski MA, Leite TFO |title=Klippel-Trenaunay and Parkes-Weber syndromes: two case reports |journal=J Vasc Bras |volume=16 |issue=4 |pages=320–324 |date=2017 |pmid=29930667 |pmc=5944310 |doi=10.1590/1677-5449.005417 |url=}}</ref>
 * [[Etiology]] and [[pathogenesis]] have not been established yet. Some suggestions include PIK3CA mutations, [[polygenic]] [[inheritance]], VG5Q mutation and obstruction of the [[venous]] system.<ref name="pmid26451379" /><ref name="pmid28458832" /><ref name="pmid29930667" />
 * [[Diagnosis]] can be made on clinical manifestations and can be confirmed by [[Doppler ultrasound]] and [[magnetic resonance angiography]]. Management depends on clinical manifestations.<ref name="pmid28458832" /><ref name="pmid29930667" /><ref name="pmid25293688" /><ref name="pmid28458832" />
@@ Line 233: / Line 233: @@
 ===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]].
+*  Characterized by a [[cutaneous]] flush with underlying multiple micro-AVFs ([[Arteriovenous fistula|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]].
 For more information on [[Parkes Weber syndrome]], [[Parkes Weber syndrome#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]].<ref name="pmid18454870">{{cite journal |vauthors=Karuppal R, Raman RV, Valsalan BP, Gopakumar Ts, Kumaran CM, Vasu CK |title=Servelle-Martorell syndrome with extensive upper limb involvement: a case report |journal=J Med Case Rep |volume=2 |issue= |pages=142 |date=May 2008 |pmid=18454870 |pmc=2394530 |doi=10.1186/1752-1947-2-142 |url=}}</ref>
+* 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.<ref name="pmid18454870">{{cite journal |vauthors=Karuppal R, Raman RV, Valsalan BP, Gopakumar Ts, Kumaran CM, Vasu CK |title=Servelle-Martorell syndrome with extensive upper limb involvement: a case report |journal=J Med Case Rep |volume=2 |issue= |pages=142 |date=May 2008 |pmid=18454870 |pmc=2394530 |doi=10.1186/1752-1947-2-142 |url=}}</ref>
 * 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.<ref name="pmid18454870" />
-* 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]].<ref name="pmid18454870" /><ref name="pmid6284617">{{cite journal |vauthors=Langer M, Langer R |title=[Radiologic aspects of the congenital arteriovenous malformations, Klippel-Trenaunay type, and Servelle-Martorell type (author's transl)] |language=German |journal=Rofo |volume=136 |issue=5 |pages=577–82 |date=May 1982 |pmid=6284617 |doi=10.1055/s-2008-1056105 |url=}}</ref>
+* 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]].<ref name="pmid18454870" /><ref name="pmid6284617">{{cite journal |vauthors=Langer M, Langer R |title=[Radiologic aspects of the congenital arteriovenous malformations, Klippel-Trenaunay type, and Servelle-Martorell type (author's transl)] |language=German |journal=Rofo |volume=136 |issue=5 |pages=577–82 |date=May 1982 |pmid=6284617 |doi=10.1055/s-2008-1056105 |url=}}</ref>
 ===Sturge-Weber syndrome===
@@ Line 249: / Line 249: @@
 ===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]].<ref name="pmid25777744">{{cite journal |vauthors=McCarthy CM, Blecher H, Reich S |title=A case of myelopathy because of enchondromas from Maffucci syndrome with successful surgical treatment |journal=Spine J |volume=15 |issue=6 |pages=e15–9 |date=June 2015 |pmid=25777744 |doi=10.1016/j.spinee.2015.03.006 |url=}}</ref><ref name="pmid26628708">{{cite journal |vauthors=Tsao YP, Tsai CY, Chen WS |title=Maffucci Syndrome |journal=J. Rheumatol. |volume=42 |issue=12 |pages=2434–5 |date=December 2015 |pmid=26628708 |doi=10.3899/jrheum.150216 |url=}}</ref><ref name="pmid26920730">{{cite journal |vauthors=Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H |title=Maffucci syndrome and neoplasms: a case report and review of the literature |journal=BMC Res Notes |volume=9 |issue= |pages=126 |date=February 2016 |pmid=26920730 |pmc=4769492 |doi=10.1186/s13104-016-1913-x |url=}}</ref>
+* 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 [[Maffucci syndrome]]. People with [[Maffucci 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]].<ref name="pmid25777744">{{cite journal |vauthors=McCarthy CM, Blecher H, Reich S |title=A case of myelopathy because of enchondromas from Maffucci syndrome with successful surgical treatment |journal=Spine J |volume=15 |issue=6 |pages=e15–9 |date=June 2015 |pmid=25777744 |doi=10.1016/j.spinee.2015.03.006 |url=}}</ref><ref name="pmid26628708">{{cite journal |vauthors=Tsao YP, Tsai CY, Chen WS |title=Maffucci Syndrome |journal=J. Rheumatol. |volume=42 |issue=12 |pages=2434–5 |date=December 2015 |pmid=26628708 |doi=10.3899/jrheum.150216 |url=}}</ref><ref name="pmid26920730">{{cite journal |vauthors=Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H |title=Maffucci syndrome and neoplasms: a case report and review of the literature |journal=BMC Res Notes |volume=9 |issue= |pages=126 |date=February 2016 |pmid=26920730 |pmc=4769492 |doi=10.1186/s13104-016-1913-x |url=}}</ref>
-* [[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]].<ref name="pmid24344754">{{cite journal |vauthors=Moriya K, Kaneko MK, Liu X, Hosaka M, Fujishima F, Sakuma J, Ogasawara S, Watanabe M, Sasahara Y, Kure S, Kato Y |title=IDH2 and TP53 mutations are correlated with gliomagenesis in a patient with Maffucci syndrome |journal=Cancer Sci. |volume=105 |issue=3 |pages=359–62 |date=March 2014 |pmid=24344754 |pmc=4317937 |doi=10.1111/cas.12337 |url=}}</ref><ref name="pmid22057234">{{cite journal |vauthors=Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV |title=Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome |journal=Nat. Genet. |volume=43 |issue=12 |pages=1256–61 |date=November 2011 |pmid=22057234 |pmc=3427908 |doi=10.1038/ng.1004 |url=}}</ref>
+* [[Mutations]] in [[Isocitrate dehydrogenase|isocitrate dehydrogenase 1]] (IDH1) and [[Isocitrate dehydrogenase|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 [[Maffucci syndrome]].<ref name="pmid24344754">{{cite journal |vauthors=Moriya K, Kaneko MK, Liu X, Hosaka M, Fujishima F, Sakuma J, Ogasawara S, Watanabe M, Sasahara Y, Kure S, Kato Y |title=IDH2 and TP53 mutations are correlated with gliomagenesis in a patient with Maffucci syndrome |journal=Cancer Sci. |volume=105 |issue=3 |pages=359–62 |date=March 2014 |pmid=24344754 |pmc=4317937 |doi=10.1111/cas.12337 |url=}}</ref><ref name="pmid22057234">{{cite journal |vauthors=Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV |title=Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome |journal=Nat. Genet. |volume=43 |issue=12 |pages=1256–61 |date=November 2011 |pmid=22057234 |pmc=3427908 |doi=10.1038/ng.1004 |url=}}</ref>
 * [[Patients]] should be evaluated to check for [[malignant]] [[transformation]]. Some recommend [[CT scans]] and [[PET scans]] at regular intervals.<ref name="pmid26920730" /><ref name="pmid26628708" /><ref name="pmid25537758">{{cite journal |vauthors=Al-Katib S, Al-Faham Z, Grant P, Palka JC |title=The Appearance of Maffucci Syndrome on 18F-FDG PET/CT |journal=J Nucl Med Technol |volume=43 |issue=2 |pages=131–2 |date=June 2015 |pmid=25537758 |doi=10.2967/jnmt.114.146480 |url=}}</ref><ref name="pmid26920730" />
 For more information on [[Maffucci syndrome]], [[Maffucci syndrome#Maffucci syndrome|click here]].
@@ Line 256: / Line 256: @@
 ===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]].<ref name="pmid25044986">{{cite journal |vauthors=Emrick LT, Murphy L, Shamshirsaz AA, Ruano R, Cassady CI, Liu L, Chang F, Sutton VR, Li M, Van den Veyver IB |title=Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes |journal=Am. J. Med. Genet. A |volume=164A |issue=10 |pages=2633–7 |date=October 2014 |pmid=25044986 |pmc=4496426 |doi=10.1002/ajmg.a.36672 |url=}}</ref><ref name="pmid25400966">{{cite journal |vauthors=Sarici D, Akin MA, Kurtoglu S, Tubas F, Sarici SU |title=A Neonate with CLOVES Syndrome |journal=Case Rep Pediatr |volume=2014 |issue= |pages=845074 |date=2014 |pmid=25400966 |pmc=4221976 |doi=10.1155/2014/845074 |url=}}</ref><ref name="pmid20537357">{{cite journal |vauthors=Alomari AI, Burrows PE, Lee EY, Hedequist DJ, Mulliken JB, Fishman SJ |title=CLOVES syndrome with thoracic and central phlebectasia: increased risk of pulmonary embolism |journal=J. Thorac. Cardiovasc. Surg. |volume=140 |issue=2 |pages=459–63 |date=August 2010 |pmid=20537357 |doi=10.1016/j.jtcvs.2010.04.023 |url=}}</ref><ref name="pmid25709171">{{cite journal |vauthors=Gopal B, Keshava SN, Selvaraj D |title=A rare newly described overgrowth syndrome with vascular malformations-Cloves syndrome |journal=Indian J Radiol Imaging |volume=25 |issue=1 |pages=71–3 |date=2015 |pmid=25709171 |pmc=4329693 |doi=10.4103/0971-3026.150166 |url=}}</ref>
-* 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]].<ref name="pmid25044986" /><ref name="pmid25709171" /><ref name="pmid20537357" />
+* Clinical and [[imaging]] findings may include swellings due to lipomatous growths, [[skin]] discoloration, [[Port-wine stain|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]].<ref name="pmid25044986" /><ref name="pmid25709171" /><ref name="pmid20537357" />
 * 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]].<ref name="pmid25044986" /><ref name="pmid25400966" /><ref name="pmid22658544">{{cite journal |vauthors=Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML |title=Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome |journal=Am. J. Hum. Genet. |volume=90 |issue=6 |pages=1108–15 |date=June 2012 |pmid=22658544 |pmc=3370283 |doi=10.1016/j.ajhg.2012.05.006 |url=}}</ref>
-* 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.<ref name="pmid25044986" /><ref name="pmid25400966" />
+* 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]].<ref name="pmid25044986" /><ref name="pmid25400966" />
 ===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]].<ref name="pmid29166516">{{cite journal |vauthors=Rocha RCC, Estrella MPS, Amaral DMD, Barbosa AM, Abreu MAMM |title=Proteus syndrome |journal=An Bras Dermatol |volume=92 |issue=5 |pages=717–720 |date=2017 |pmid=29166516 |pmc=5674710 |doi=10.1590/abd1806-4841.20174496 |url=}}</ref><ref name="pmid28377973">{{cite journal |vauthors=El-Sobky TA, Elsayed SM, El Mikkawy DM |title=Orthopaedic manifestations of Proteus syndrome in a child with literature update |journal=Bone Rep |volume=3 |issue= |pages=104–108 |date=December 2015 |pmid=28377973 |pmc=5365241 |doi=10.1016/j.bonr.2015.09.004 |url=}}</ref><ref name="pmid25377688">{{cite journal |vauthors=Hannoush H, Sachdev V, Brofferio A, Arai AE, LaRocca G, Sapp J, Sidenko S, Brenneman C, Biesecker LG, Keppler-Noreuil KM |title=Myocardial fat overgrowth in Proteus syndrome |journal=Am. J. Med. Genet. A |volume=167A |issue=1 |pages=103–10 |date=January 2015 |pmid=25377688 |pmc=4275354 |doi=10.1002/ajmg.a.36773 |url=}}</ref>
+* [[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]].<ref name="pmid29166516">{{cite journal |vauthors=Rocha RCC, Estrella MPS, Amaral DMD, Barbosa AM, Abreu MAMM |title=Proteus syndrome |journal=An Bras Dermatol |volume=92 |issue=5 |pages=717–720 |date=2017 |pmid=29166516 |pmc=5674710 |doi=10.1590/abd1806-4841.20174496 |url=}}</ref><ref name="pmid28377973">{{cite journal |vauthors=El-Sobky TA, Elsayed SM, El Mikkawy DM |title=Orthopaedic manifestations of Proteus syndrome in a child with literature update |journal=Bone Rep |volume=3 |issue= |pages=104–108 |date=December 2015 |pmid=28377973 |pmc=5365241 |doi=10.1016/j.bonr.2015.09.004 |url=}}</ref><ref name="pmid25377688">{{cite journal |vauthors=Hannoush H, Sachdev V, Brofferio A, Arai AE, LaRocca G, Sapp J, Sidenko S, Brenneman C, Biesecker LG, Keppler-Noreuil KM |title=Myocardial fat overgrowth in Proteus syndrome |journal=Am. J. Med. Genet. A |volume=167A |issue=1 |pages=103–10 |date=January 2015 |pmid=25377688 |pmc=4275354 |doi=10.1002/ajmg.a.36773 |url=}}</ref>
-* 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]].<ref name="pmid29166516" /><ref name="pmid28377973" /><ref name="pmid25377688" /><ref name="pmid24882963">{{cite journal |vauthors=Sarman ZS, Yuksel N, Sarman H, Bayramgurler D |title=Proteus syndrome: report of a case with developmental glaucoma |journal=Korean J Ophthalmol |volume=28 |issue=3 |pages=272–4 |date=June 2014 |pmid=24882963 |pmc=4038735 |doi=10.3341/kjo.2014.28.3.272 |url=}}</ref>
+* 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]].<ref name="pmid29166516" /><ref name="pmid28377973" /><ref name="pmid25377688" /><ref name="pmid24882963">{{cite journal |vauthors=Sarman ZS, Yuksel N, Sarman H, Bayramgurler D |title=Proteus syndrome: report of a case with developmental glaucoma |journal=Korean J Ophthalmol |volume=28 |issue=3 |pages=272–4 |date=June 2014 |pmid=24882963 |pmc=4038735 |doi=10.3341/kjo.2014.28.3.272 |url=}}</ref>
-* 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.<ref name="pmid25377688" /><ref name="pmid26657992">{{cite journal |vauthors=Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG |title=Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome |journal=Sci Rep |volume=5 |issue= |pages=17162 |date=December 2015 |pmid=26657992 |pmc=4675973 |doi=10.1038/srep17162 |url=}}</ref>
+* 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.<ref name="pmid25377688" /><ref name="pmid26657992">{{cite journal |vauthors=Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG |title=Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome |journal=Sci Rep |volume=5 |issue= |pages=17162 |date=December 2015 |pmid=26657992 |pmc=4675973 |doi=10.1038/srep17162 |url=}}</ref>
 * [[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.<ref name="pmid29166516" /><ref name="pmid22876373">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Biesecker LG, Sapp JC |title= |journal= |volume= |issue= |pages= |date= |pmid=22876373 |doi= |url=}}</ref>
 For more information about [[Proteus syndrome]], [[Proteus syndrome#Proteus syndrome|click here]].
@@ Line 269: / Line 269: @@
 ===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.<ref name="pmid24474112">{{cite journal |vauthors=Gontijo GM, Pinto CA, Rogatto SR, Cunha IW, Aguiar S, Alves CA |title=Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant--case report |journal=An Bras Dermatol |volume=88 |issue=6 |pages=982–5 |date=2013 |pmid=24474112 |pmc=3900354 |doi=10.1590/abd1806-4841.20132730 |url=}}</ref><ref name="pmid24379037">{{cite journal |vauthors=Peiretti V, Mussa A, Feyles F, Tuli G, Santanera A, Molinatto C, Ferrero GB, Corrias A |title=Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome |journal=J Clin Res Pediatr Endocrinol |volume=5 |issue=4 |pages=261–5 |date=2013 |pmid=24379037 |pmc=3890226 |doi=10.4274/Jcrpe.984 |url=}}</ref><ref name="pmid26157835">{{cite journal |vauthors=Sagi SV, Ballard DD, Marks RA, Dunn KR, Kahi CJ |title=Bannayan Ruvalcaba Riley Syndrome |journal=ACG Case Rep J |volume=1 |issue=2 |pages=90–2 |date=January 2014 |pmid=26157835 |pmc=4435287 |doi=10.14309/crj.2014.11 |url=}}</ref>
-* 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]].<ref name="pmid24474112" /><ref name="pmid24379037" /><ref name="pmid26157835" />
+* 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|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]].<ref name="pmid24474112" /><ref name="pmid24379037" /><ref name="pmid26157835" />
-* [[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.<ref name="pmid24474112" />
+* [[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|autosomal-dominant]] transmission and sporadic occurrence have been reported.<ref name="pmid24474112" />
-* [[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]].<ref name="pmid24474112" /><ref name="pmid26157835" />
+* [[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]].<ref name="pmid24474112" /><ref name="pmid26157835" />
 For more information on Bannayan-Riley-Ruvalcaba syndrome, [[Bannayan-Zonana syndrome#Bannayan-Zonana syndrome|click here]].

Vascular malformation: Difference between revisions

Latest revision as of 19:25, 26 October 2018

Overview

Classification

Simple Vascular Malformations

Combined Vascular Malformations

Vascular Malformations of Major Named Vessels

Vascular Malformations associated With other Anomalies

Klippel-Trenaunay syndrome

Parkes Weber syndrome

Servelle-Martorell syndrome

Sturge-Weber syndrome

Maffucci syndrome

CLOVES syndrome

Proteus syndrome

Bannayan-Riley-Ruvalcaba syndrome

CLAPO syndrome

See also

References

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Vascular malformation
Classification and external resources
MeSH	D054079