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Genetics Home Reference: your guide to understanding genetic conditions
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Milroy disease

Reviewed April 2013

What is Milroy disease?

Milroy disease is a condition that affects the normal function of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema). Individuals with Milroy disease typically have lymphedema in their lower legs and feet at birth or develop it in infancy. The lymphedema typically occurs on both sides of the body and may worsen over time.

Milroy disease is associated with other features in addition to lymphedema. Males with Milroy disease are sometimes born with an accumulation of fluid in the scrotum (hydrocele). Males and females may have upslanting toenails, deep creases in the toes, wart-like growths (papillomas), and prominent leg veins. Some individuals develop non-contagious skin infections called cellulitis that can damage the thin tubes that carry lymph fluid (lymphatic vessels). Episodes of cellulitis can cause further swelling in the lower limbs.

How common is Milroy disease?

Milroy disease is a rare disorder; its incidence is unknown.

What genes are related to Milroy disease?

Mutations in the FLT4 gene cause some cases of Milroy disease. The FLT4 gene provides instructions for producing a protein called vascular endothelial growth factor receptor 3 (VEGFR-3), which regulates the development and maintenance of the lymphatic system. Mutations in the FLT4 gene interfere with the growth, movement, and survival of cells that line the lymphatic vessels (lymphatic endothelial cells). These mutations lead to the development of small or absent lymphatic vessels. If lymph fluid is not properly transported, it builds up in the body's tissues and causes lymphedema. It is not known how mutations in the FLT4 gene lead to the other features of this disorder.

Many individuals with Milroy disease do not have a mutation in the FLT4 gene. In these individuals, the cause of the disorder is unknown.

Related Gene(s)

Changes in this gene are associated with Milroy disease.

  • FLT4

How do people inherit Milroy disease?

Milroy disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the FLT4 gene. These cases occur in people with no history of the disorder in their family. About 10 percent to 15 percent of people with a mutation in the FLT4 gene do not develop the features of Milroy disease.

Where can I find information about diagnosis or management of Milroy disease?

These resources address the diagnosis or management of Milroy disease and may include treatment providers.

  • Gene Review: Milroy Disease (http://www.ncbi.nlm.nih.gov/books/NBK1239)
  • Genetic Testing Registry: Hereditary lymphedema type I (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1704423)
  • MedlinePlus Encyclopedia: Lymphatic Obstruction (http://www.nlm.nih.gov/medlineplus/ency/article/001117.htm)

You might also find information on the diagnosis or management of Milroy disease in Educational resources (http://ghr.nlm.nih.gov/condition/milroy-disease/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/milroy-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Milroy disease?

You may find the following resources about Milroy disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Milroy disease?

  • congenital familial lymphedema
  • hereditary lymphedema type I
  • Milroy's disease
  • Nonne-Milroy lymphedema

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Milroy disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Milroy disease?

autosomal ; autosomal dominant ; cell ; congenital ; endothelial cells ; familial ; gene ; growth factor ; hereditary ; incidence ; inherited ; lymph ; lymphatic system ; lymphedema ; mutation ; protein ; receptor ; scrotum ; vascular ; veins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • 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 Feb;42(2):98-102. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15689446?dopt=Abstract)
  • Butler MG, Dagenais SL, Rockson SG, Glover TW. A novel VEGFR3 mutation causes Milroy disease. Am J Med Genet A. 2007 Jun 1;143A(11):1212-7. (http://www.ncbi.nlm.nih.gov/pubmed/17458866?dopt=Abstract)
  • Evans AL, Bell R, Brice G, Comeglio P, Lipede C, Jeffery S, Mortimer P, Sarfarazi M, Child AH. Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema. J Med Genet. 2003 Sep;40(9):697-703. (http://www.ncbi.nlm.nih.gov/pubmed/12960217?dopt=Abstract)
  • Gene Review: Milroy Disease (http://www.ncbi.nlm.nih.gov/books/NBK1239)
  • Ghalamkarpour A, Morlot S, Raas-Rothschild A, Utkus A, Mulliken JB, Boon LM, Vikkula M. Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. Clin Genet. 2006 Oct;70(4):330-5. (http://www.ncbi.nlm.nih.gov/pubmed/16965327?dopt=Abstract)
  • Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet. 2000 Aug;67(2):295-301. Epub 2000 Jun 9. (http://www.ncbi.nlm.nih.gov/pubmed/10856194?dopt=Abstract)
  • 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 Jun;25(2):153-9. (http://www.ncbi.nlm.nih.gov/pubmed/10835628?dopt=Abstract)
  • Levinson KL, Feingold E, Ferrell RE, Glover TW, Traboulsi EI, Finegold DN. Age of onset in hereditary lymphedema. J Pediatr. 2003 Jun;142(6):704-8. (http://www.ncbi.nlm.nih.gov/pubmed/12838201?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2013
Published: October 27, 2014