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Lymphedema-distichiasis syndrome

Reviewed February 2014

What is lymphedema-distichiasis syndrome?

Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system, which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. People with lymphedema-distichiasis syndrome develop puffiness or swelling (lymphedema) of the limbs, typically the legs and feet. Another characteristic of this syndrome is the growth of extra eyelashes (distichiasis), ranging from a few extra eyelashes to a full extra set on both the upper and lower lids. These eyelashes do not grow along the edge of the eyelid, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Related eye problems can include an irregular curvature of the cornea causing blurred vision (astigmatism) or scarring of the cornea. Other health problems associated with this disorder include swollen and knotted (varicose) veins, droopy eyelids (ptosis), heart abnormalities, and an opening in the roof of the mouth (a cleft palate).

All people with lymphedema-distichiasis syndrome have extra eyelashes present at birth. The age of onset of lymphedema varies, but it most often begins during puberty. Males usually develop lymphedema earlier than females, but all affected individuals will develop lymphedema by the time they are in their forties.

How common is lymphedema-distichiasis syndrome?

The prevalence of lymphedema-distichiasis syndrome is unknown. Because the extra eyelashes can be overlooked during a medical examination, researchers believe that some people with this condition may be misdiagnosed as having lymphedema only.

What genes are related to lymphedema-distichiasis syndrome?

Lymphedema-distichiasis syndrome is caused by mutations in the FOXC2 gene. The FOXC2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. The FOXC2 protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. Researchers believe that the FOXC2 protein has a role in a variety of developmental processes, such as the formation of veins and the development of the lungs, eyes, kidneys and urinary tract, cardiovascular system, and the transport system for immune cells (lymphatic vessels).

Related Gene(s)

Changes in this gene are associated with lymphedema-distichiasis syndrome.

  • FOXC2

How do people inherit lymphedema-distichiasis syndrome?

This condition 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 some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of lymphedema-distichiasis syndrome?

These resources address the diagnosis or management of lymphedema-distichiasis syndrome and may include treatment providers.

  • Gene Review: Lymphedema-Distichiasis Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1457/)
  • Genetic Testing Registry: Distichiasis-lymphedema syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265345)
  • MedlinePlus Encyclopedia: Lymph System (http://www.nlm.nih.gov/medlineplus/ency/article/002247.htm)

You might also find information on the diagnosis or management of lymphedema-distichiasis syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/lymphedema-distichiasis-syndrome/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 lymphedema-distichiasis syndrome?

You may find the following resources about lymphedema-distichiasis syndrome 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 lymphedema-distichiasis syndrome?

  • distichiasis-lymphedema syndrome
  • lymphedema with distichiasis

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 lymphedema-distichiasis syndrome?

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

What glossary definitions help with understanding lymphedema-distichiasis syndrome?

astigmatism ; autosomal ; autosomal dominant ; cardiovascular ; cell ; cleft palate ; cornea ; DNA ; gene ; inherited ; lymphatic system ; lymphedema ; mutation ; palate ; prevalence ; protein ; ptosis ; puberty ; syndrome ; transcription ; transcription factor ; veins

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

References

  • 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 Jul;39(7):478-83. (http://www.ncbi.nlm.nih.gov/pubmed/12114478?dopt=Abstract)
  • Erickson RP, Dagenais SL, Caulder MS, Downs CA, Herman G, Jones MC, Kerstjens-Frederikse WS, Lidral AC, McDonald M, Nelson CC, Witte M, Glover TW. Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations. J Med Genet. 2001 Nov;38(11):761-6. (http://www.ncbi.nlm.nih.gov/pubmed/11694548?dopt=Abstract)
  • Fang J, Dagenais SL, Erickson RP, Arlt MF, Glynn MW, Gorski JL, Seaver LH, Glover TW. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet. 2000 Dec;67(6):1382-8. Epub 2000 Nov 8. (http://www.ncbi.nlm.nih.gov/pubmed/11078474?dopt=Abstract)
  • Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S, Levick JR, Burnand KG, Mortimer PS; Lymphoedema Research Consortium. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation. 2007 Apr 10;115(14):1912-20. Epub 2007 Mar 19. (http://www.ncbi.nlm.nih.gov/pubmed/17372167?dopt=Abstract)
  • Sutkowska E, Bator A, Trompeta K, Szuba A. Different lymphscintigraphic patterns in patients with lymphedema distichiasis. Lymphology. 2010 Jun;43(2):73-7. (http://www.ncbi.nlm.nih.gov/pubmed/20848994?dopt=Abstract)
  • Vreeburg M, Heitink MV, Damstra RJ, Moog U, van Geel M, van Steensel MA. Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene. Int J Dermatol. 2008 Nov;47 Suppl 1:52-5. doi: 10.1111/j.1365-4632.2008.03962.x. (http://www.ncbi.nlm.nih.gov/pubmed/18986489?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: February 2014
Published: August 25, 2014