Jornal Vascular Brasileiro
https://app.periodikos.com.br/journal/jvb/article/doi/10.1590/S1677-54492008000300011
Jornal Vascular Brasileiro
Review Article

Linfangiogênese e genética dos linfedemas: revisão da literatura

Lymphangiogenesis and genetics in lymphedemas: a review of the literature

Mauro Andrade

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Resumo

O estudo do genoma humano propiciou recentes descobertas de genes e de complexos mecanismos de controle da linfangiogênese. Neste artigo esses conhecimentos são revistos, com suas implicações na embriogênese e desenvolvimento do sistema linfático e na etiopatogenia de diferentes formas e síndromes de linfedema hereditário. Algumas doenças linfáticas de transmissão genética e síndromes de aneuploidia são descritas nas suas características genotípicas e fenotípicas. Os avanços na compreensão do crescimento e desenvolvimento dos vasos linfáticos devem trazer novas alternativas terapêuticas nas linfangiodisplasias e no controle da disseminação linfática dos tumores.

Palavras-chave

Linfedema, genética, linfangiogênese

Abstract

Recent advances in the exploration and manipulation of the human genome provided new insights into the intricate genetics and control of lymphangiogenesis. Implications for embryogenesis and development of the lymphatic system and its role in some familial and aneuploid syndromes are reviewed, along with their genotypic and phenotypic characteristics. Increased understanding of growth and development of the lymphatic vessels may bring new therapeutic options for lymphatic angiodysplasias and control of the lymphatic spread of tumors.

Keywords

Lymphedema, genetics, lymphangiogenesis

References

Milroy WF. An undescribed variety of hereditary edema. N Y Med J. 1892;56:505-8.

Tille JC, Pepper MS. Hereditary vascular anomalies: new insights into their pathogenesis. Arterioscler Thromb Vasc Biol. 2004;24:1578-90.

Sabin F. On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig. Am J Anat. 1902;1:367-91.

Huntington GS, McClure CF. The anatomy and development of the jugular lymph sac in the domestic cat (Felis domestica). Am J Anat. 1910;10:177-311.

Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98:769-78.

Schneider M, Othman-Hassan K, Christ B, Wilting J. Lymphangioblasts in the avian wing bud. Dev Dyn. 1999;216:311-9.

Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors. Nat Med. 1999;5:1359-64.

Dumont DJ, Jussila L, Taipale JL. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 1998;282:946-9.

Jussila L, Alitalo K. Vascular growth factors and lymphangiogenesis. Physiol Rev. 2002;82:673-700.

Kaipainen A, Korhonen J, Mustonen T. Expression of the fms-like tyrosine kinase FLT4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci. USA. 1995;92:3566-70.

Petrova TV, Makinen T, Alitalo K. Signaling via vascular endothelial growth factor receptors. Exp Cell Res. 1999;253:117-30.

Karkkainen M, Saaristo A, Jussila L. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci. USA. 2001;98:12677-82.

On Line Mendelian Inheritance in Man. .

Witte MH, Way DL, Witte CL, Bernas M. Lymphangiogenesis: mechanisms, significance and clinical implications. Regulation of angiogenesis. 1997:65-112.

Morgan T. Turner syndrome: diagnosis and management. Am Fam Physician. 2007;76:405-10.

Chevernak FA, Issacson G, Blakemore KJ. Fetal cystic hygrome: Cause and natural history. N Engl J Med. 1983;309:822-5.

Boucher CA, Sargent CA, Ogata T, Affara NA. Breakpoint analysis of Turner patients with partial Xp deletions: implications for the lymphoedema gene location. J Med Genet. 2001;38:591-8.

Witte MH, Erickson R, Reiser FA, Witte CL. Genetic alterations in lymphedema. Phlebolymphology. 1997;16:19-25.

Witte MH, Erickson R, Bernas M. Phenotypic and genotypic heterogeneity in familial Milroy lymphedema. Lymphology. 1998;31:145-55.

Ferrell RE, Levinson KL, Esman JH. Hereditary lymphoedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. 1998;7:2073-8.

Holberg CJ, Erickson RP, Bernas MJ. Segregation analyses and a genome-wide linkage search confirm genetic heterogeneity and suggest oligogenic inheritance in some Milroy congenital primary lymphedema families. Am J Med Genet. 2001;98:303-12.

Karkkainen MJ, Ferrell RE, Lawrence EC. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000;25:153-9.

Karkkainen MJ, Saaristo A, Jussila L. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A. 2001;98:12677-82.

Fink AM, Kaltenegger I, Schneider B, Frühauf J, Jurecka W, Steiner A. Serum level of VEGF-D in patients with primary lymphedema. Lymphology. 2004;37:185-9.

Meige H. Dystrophie oedemateuse héreditaire. Presse Med. 1898;6:341-3.

Burnand KG, Mortimer PS. Lymphangiogenesis and genetics of lymphoedema. Diseases of the lymphatics. 2003:102-9.

Northrup KA, Witte MH, Witte CL. Syndromic classification of hereditary lymphedema. Lymphology. 2003;36:162-89.

Browse NL, Stewart G. Lymphoedema: pathophysiology and classification. J Cardiovasc Surg (Torino). 1985;26:91-106.

Rosbotham JL, Brice GW, Child AH, Nunan TO, Mortimer PS, Burnand KG. Distichiasis-lymphoedema: clinical features, venous function and lymphoscintigraphy. Br J Dermatol. 2000;142.

Mangion J, Rahman N, Mansour S. gene for lymphedema-distichiasis maps to 16q24.3. Am J Hum Genet. 1999;65:427-32.

Kriederman BM, Myloyde TL, Witte MH. FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. Hum Mol Genet. 2003;12:1179-85.

Iida K, Koseki H, Kakinuma H. Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis. Development. 1997;124:4627-38.

Finegold DN, Kimak MA, Lawrence EC. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet. 2001;10:1185-9.

Glade C, van Steensel MA, Steijlen PM. Hypotrichosis, lymphedema of the legs and acral telangiectasias-new syndrome?. Eur J Dermatol. 2001;11:515-7.

Irrthum A, Devriendt K, Chitayat D. Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. Am J Hum Genet. 2003;72:1470-8.

Aagenaes O, van der Hagen CB, Refsum S. Hereditary recurrent intrahepatic cholestasis from birth. Arch Dis Child. 1968;43:646-57.

Bull LN, Roche E, Song EJ. Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a 6.6-cM interval on chromosome 15q. Am J Hum Genet. 2000;67:994-9.

Witte MH, Ohkuma M, Andrade M, Campisi C, Boccardo F. Nature's historic gap: the 20th century of lymphology. Lymphology. 2005;38:157-8.

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