This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Shinawi, M. Search for Related Content PubMed PubMed Citation Articles by Shinawi, M. Social Bookmarking                         What's this?

Lymphedema of the Lower Extremity: Is It Genetic or Nongenetic?

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, mshinawi{at}bcm.tmc.edu

Lymphedema of the lower extremities is a diagnostic challenge. Exclusion of secondary causes of limb swelling and secondary lymphedema is the initial step. Primary lymphedema is classified into idiopathic and familial (hereditary) subgroups. Hereditary lymphedema can be nonsyndromic or associated with congenital anomalies or with abnormal physical findings. A 13-year-old girl presented with unilateral lower extremity lymphedema. Her medical and family history was unremarkable. The physical examination was negative for dysmorphic features and congenital anomalies. Lymphoscintigraphy showed no evidence of lymph flow in the left lower extremity, which persisted at the delayed 2-hour image. A comprehensive clinical and family history that includes a thorough physical examination are the mainstays of the medical assessment of lymphedema in children. Isotopic lymphoscintigraphy is generally considered the gold standard for confirmation of the diagnosis. This article discusses the differential diagnosis, reviews the literature, and suggests a simplified and an updated flowchart for the classification of unilateral limb lymphedema in children.

Key Words: lymphedema • syndromic • genetic • lymphoscintigraphy • lymphangiogenesis

References

• Szuba A., Rockson SG Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998;3:145-156.[Abstract/Free Full Text]
• Smeltzer DM, Stickler GB, Schirger A. Primary lymphedema in children and adolescents: a follow-up study and review. Pediatrics. 1985;76:206-218.[Abstract/Free Full Text]
• Szuba A., Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44:43-57.[Abstract/Free Full Text]
• Williams WH, Witte CL, Witte MH, McNeill GC Radionuclide lymphangioscintigraphy in the evaluation of peripheral lymphedema. Clin Nucl Med. 2000;25: 451-464.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Witte CL, Witte MH, Unger EC, et al. Advances in imaging of lymph flow disorders. Radiographics. 2000;20: 1697-1719.[Abstract/Free Full Text]
• Tiwari A., Cheng KS, Button M., Myint F., Hamilton G. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. 2003;138:152-161.[Abstract/Free Full Text]
• Northup KA, Witte MH, Witte CL Syndromic classification of hereditary lymphedema. Lymphology. 2003;36: 162-189.[Web of Science][Medline] [Order article via Infotrieve]
• An A., Rockson SG The potential for molecular treatment strategies in lymphatic disease. Lymphat Res Biol. 2004;2:173-181.[CrossRef][Medline] [Order article via Infotrieve]
• Cueni LN, Detmar M. New insights into the molecular control of the lymphatic vascular system and its role in disease. J Invest Dermatol. 2006;12:2167-2177.
• Oliver G. Lymphatic vasculature development. Nat Rev Immunol. 2004;4:35-45.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Witte MH, Bernas MJ, Martin CP, Witte CL Lymphangiogenesis and lymphangiodysplasia: from molecular to clinical lymphology. Microsc Res Tech. 2001;55:122-145.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Brice G., Child AH, Evans A., et al. Milroy disease and the VEGFR-3 mutation phenotype. J Med Genet. 2005;42: 98-102.[Abstract/Free Full Text]
• Karkkainen MJ, Ferrell RE, Lawrence EC, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000;25:153-159.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fang J., Dagenais SL, Erickson RP, et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet. 2000;67:1382-1388.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mellor RH, Brice G., Stanton AW, et al. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation. 2007;115: 1912-1920.
• Levinson KL, Feingold E., Ferrell RE, Glover TW, Traboulsi EI, Finegold DN Age of onset in hereditary lymphedema. J Pediatr. 2003;142:704-708.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Irrthum A., Devriendt K., Chitayat D., et al. Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedematelangiectasia. Am J Hum Genet. 2003;72: 1470-1478.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Finegold DN, Kimak MA, Lawrence EC, et al. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet. 2001;10:1185-1189.[Abstract/Free Full Text]
• Ruocco V., Schwartz RA, Ruocco E. Lymphedema: an immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol. 2002;47:124-127.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cerri A., Gianni C., Corbellino M., Pizzuto M., Moneghini L., Crosti C. Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema. Eur J Dermatol. 1998;8:511-514.[Web of Science][Medline] [Order article via Infotrieve]
• Rockson SG Lymphedema. Am J Med. 2001;110:288-295.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Casley-Smith JR Benzo-pyrones in the treatment of lymphoedema. Int Angiol. 1999;18:31-41.[Web of Science][Medline] [Order article via Infotrieve]
• Bernas MJ, Witte CL, Witte MH; International Society of Lymphology Executive Committee. The diagnosis and treatment of peripheral lymphedema: draft revision of the 1995 Consensus Document of the International Society of Lymphology Executive Committee for discussion at the September 3-7, 2001, XVIII International Congress of Lymphology in Genoa, Italy. Lymphology. 2001;34:84-91.
• Yoon YS, Murayama T., Gravereaux E., et al. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema. J Clin Invest. 2003,11:717-725.

This version was published on December 1, 2007

Clinical Pediatrics, Vol. 46, No. 9, 835-841 (2007)
DOI: 10.1177/0009922807303545


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Shinawi, M. Search for Related Content PubMed PubMed Citation Articles by Shinawi, M. Social Bookmarking                         What's this?