Skip to main content
SpringerLink
Log in

Etiology of Primary Lymphedema

  • Chapter
  • First Online:
Peripheral Lymphedema

  • 928 Accesses

Abstract

The clinical symptoms of primary lymphedema are diverse, and its pathogenesis is complicated. Previous studies have shown that primary lymphedema is a multi-gene-involved disease. More than 20 causative genes have been identified in patients. Newly developed imaging techniques can show morphological and functional anomalies of affected lymphatic systems. Study on the correlations between the phenotype and genotype of primary lymphedemas will uncover the complicated etiology of this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Grada AA, Phillips TJ. Lymphedema: pathophysiology and clinical manifestations. J Am Acad Dermatol. 2017;77(6):1009–20. https://doi.org/10.1016/j.jaad.2017.03.022.

    Article  PubMed  Google Scholar 

  2. Lee BB, Laredo J. Pathophysiology of primary lymphedema. In: Neligan PC, Masia J, Piller NB, editors. Lymphedema: complete medical and surgical management. CRC Press, Taylor & Francis Group; 2015. p. 177–87.

    Google Scholar 

  3. Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, Finegold DN. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. 1998;7(13):2073–8.

    Article  CAS  Google Scholar 

  4. Gordon K, Spiden SL, Connell FC, Brice G, Cottrell S, Short J, Taylor R, Jeffery S, Mortimer PS, Mansour S, Ostergaard P. FLT4/VEGFR3 and milroy disease: novel mutations, a review of published variants and database update. Hum Mutat. 2013;34(1):23–31. https://doi.org/10.1002/humu.22223.

    Article  CAS  PubMed  Google Scholar 

  5. Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000;25(2):153–9.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  7. Brice G, Child AH, Evans A, Bell R, Mansour S, Burnand K, Sarfarazi M, Jeffery S, Mortimer P. Milroy disease and the VEGFR-3 mutation phenotype. J Med Genet. 2005;42(2):98–102.

    Article  CAS  Google Scholar 

  8. Liu NF, Yu ZY, Sun D, Lou Y. Rare variants in LAMA5 gene associated with FLT4 and FOXC2 mutations in primary lymphedema may contribute to severity. Lymphology. 2016;49(4):192–204.

    CAS  PubMed  Google Scholar 

  9. Liu NF, Yu ZY, Lou Y, Sun D. A Milroy case with FLT4/VEGFR3 mutation and an unusual skin biopsy. Br J Dermatol. 2019;180(1):223–4. https://doi.org/10.1111/bjd.17120.

    Article  CAS  PubMed  Google Scholar 

  10. Michelini S, Paolacci S, Manara E, Eretta C, Mattassi R, Lee BB, Bertelli M. Genetic tests in lymphatic vascular malformations and lymphedema. J Med Genet. 2018;55(4):222–32. https://doi.org/10.1136/jmedgenet-2017-105064.

    Article  CAS  PubMed  Google Scholar 

  11. Brouillard P, Boon L, Vikkula M. Genetics of lymphatic anomalies. J Clin Invest. 2014;124(3):898–904. https://doi.org/10.1172/JCI71614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brice G, Mansour S, Bell R, Collin JR, Child AH, Brady AF, Sarfarazi M, Burnand KG, Jeffery S, Mortimer P, Murday VA. Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. J Med Genet. 2002;39(7):478–83.

    Article  CAS  Google Scholar 

  13. Finegold DN, Kimak MA, Lawrence EC, Levinson KL, Cherniske EM, Pober BR, Dunlap JW, Ferrell RE. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet. 2001;10(11):1185–9.

    Article  CAS  Google Scholar 

  14. Petrova TV, Karpanen T, Norrmén C, Mellor R, Tamakoshi T, Finegold D, Ferrell R, Kerjaschki D, Mortimer P, Ylä-Herttuala S, Miura N, Alitalo K. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med. 2004;10(9):974–81.

    Article  CAS  Google Scholar 

  15. Lukacs V, Mathur J, Mao R, Bayrak-Toydemir P, Procter M, Cahalan SM, Kim HJ, Bandell M, Longo N, Day RW, Stevenson DA, Patapoutian A, Krock BL. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphaticdysplasia. Nat Commun. 2015;21(6):8329. https://doi.org/10.1038/ncomms9329.

    Article  CAS  Google Scholar 

  16. Andolfo I, De Rosa G, Errichiello E, Manna F, Rosato BE, Gambale A, Vetro A, Calcaterra V, Pelizzo G, De Franceschi L, Zuffardi O, Russo R, Iolascon A. PIEZO1 hypomorphic variants in congenital lymphatic dysplasia cause shape and hydration alterations of red blood cells. Front Physiol. 2019;15(10):258. https://doi.org/10.3389/fphys.2019.00258.

    Article  Google Scholar 

  17. Liu NF, Yu Z, Luo Y, Sun D. A LYVE-1/CRSBP-1 mutation in inherited primary lymphedema. Lymphology. 2017;50(1):9–15.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Ningfei Liu

Authors
  1. Ningfei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth Peolple’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Ningfei Liu

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Liu, N. (2021). Etiology of Primary Lymphedema. In: Liu, N. (eds) Peripheral Lymphedema. Springer, Singapore. https://doi.org/10.1007/978-981-16-3484-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-981-16-3484-0_6

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-3483-3

  • Online ISBN: 978-981-16-3484-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation