Extracranial arterial venous malformations (eAVM) are AVMs that are not in the brain or spine. They can be on the head and neck, extremities, or other organs and can cause significant bleeding, alteration, heart failure, and pain. These are abnormal connections between the arteries and the veins that are caused by germline or somatic mutations mostly of the Ras pathway.
Phenotypic features: Erythematous warm pulsatile area with increase in soft tissue. Area can be deep or superficial. Diagnosis can be made at any age. Area of erythema is sometimes misdiagnosed as a capillary malformation
Excludes AVM of the central nervous system.
Genetics: Associated with somatic mutations in MAP2K1/RAS/RAF signaling pathway proteins: including MAP2K1, KRAS, BRAF,HRAS and other gain of function mutations.
Symptoms: Pounding or pulsating sensation, pain, bleeding, ulcerations, infection, swelling, decreased functionality.
Treatment: Traditionally treated by procedural intervention but rarely cured. Medical options being investigated.
References
Keppler-Noreuil KM, Rios JJ, Parker VE, Semple RK, Lindhurst MJ, Sapp JC, Alomari A, Ezaki M, Dobyns W, Biesecker LG. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015 Feb;167A(2):287-95. doi: 10.1002/ajmg.a.36836. Epub 2014 Dec 31. PMID: 25557259; PMCID: PMC4480633.
Qiao C, Richter GT, Pan W, Jin Y, Lin X. Extracranial arteriovenous malformations: from bedside to bench. Mutagenesis. 2019 Dec 19;34(4):299-306. doi: 10.1093/mutage/gez028. PMID: 31613971.
Borst AJ, Britt A, Adams DM. Complex lymphatic anomalies: Molecular landscape and medical management. Semin Pediatr Surg. 2024 Jun;33(3):151422. doi: 10.1016/j.sempedsurg.2024.151422. Epub 2024 May 22. PMID: 38833763.
Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, Burrows P, Frieden IJ, Garzon MC, Lopez-Gutierrez JC, Lord DJ, Mitchel S, Powell J, Prendiville J, Vikkula M; ISSVA Board and Scientific Committee. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies. Pediatrics. 2015 Jul;136(1):e203-14. doi: 10.1542/peds.2014-3673. Epub 2015 Jun 8. PMID: 26055853.
Kunimoto K, Yamamoto Y, Jinnin M. ISSVA Classification of Vascular Anomalies and Molecular Biology. Int J Mol Sci. 2022 Feb 21;23(4):2358. doi: 10.3390/ijms23042358. PMID: 35216474; PMCID: PMC8876303.
Reynolds G, Cardaropoli S, Carli D, Luca M, Gazzin A, Coppo P, La Selva R, Piglionica M, Bagnulo R, Turchiano A, Ranieri C, Resta N, Mussa A. Epidemiology of the disorders of the Pik3ca-related overgrowth spectrum (Pros). Eur J Hum Genet. 2023 Nov;31(11):1333-1336. doi: 10.1038/s41431-023-01414-9. Epub 2023 Jun 26. PMID: 37365400; PMCID: PMC10620148.
Penington A, Phillips RJ, Sleebs N, Halliday J. Estimate of the Prevalence of Vascular Malformations. Journal of Vascular Anomalies. 4(3):p e068, September 2023. | DOI: 10.1097/JOVA.0000000000000068
Ryu JY, Chang YJ, Lee JS, Choi KY, Yang JD, Lee SJ, Lee J, Huh S, Kim JY, Chung HY. A nationwide cohort study on incidence and mortality associated with extracranial vascular malformations. Sci Rep. 2023 Aug 25;13(1):13950. doi: 10.1038/s41598-023-41278-z. PMID: 37626114; PMCID: PMC10457363.
Rosenberg M. Most Populous Metropolitan Areas in the United States. ThoughtCo. Jun. 7, 2024.
Montez JK, Beckfield J, Cooney JK, Grumbach JM, Hayward MD, Koytak HZ, Woolf SH, Zajacova A. US State Policies, Politics, and Life Expectancy. Milbank Q. 2020 Sep;98(3):668-699. doi: 10.1111/1468-0009.12469. Epub 2020 Aug 4. PMID: 32748998; PMCID: PMC7482386.
Lawton MT, Rutledge WC, Kim H, Stapf C, Whitehead KJ, Li DY, Krings T, terBrugge K, Kondziolka D, Morgan MK, Moon K, Spetzler RF. Brain arteriovenous malformations. Nat Rev Dis Primers. 2015 May 28;1:15008. doi: 10.1038/nrdp.2015.8. PMID: 27188382.