Genetic Testing for Lymphatic Disease

Inherited forms of lymphedema are not common, but not rare. There is often a female predominance, with female:male ratios estimated to be between 2.5:1 and 10:1.

There are now several inherited forms of lymphedema for which a specific mutation has been identified. Genetic testing is available for these mutations:

Milroy's Disease, which is familial lymphedema that is present at birth, was originally
described in 1892. In some families, this disorder has been linked to the gene known as
 FLT4. This gene is responsible for one of the early steps in lymphatic development.

Lymphedema-distichiasis is another, distinct form of inherited lymphedema. This syndrome typically appears at or after the onset of puberty in affected individuals.

The lymphedema characteristically affects the region of the legs closer to the feet, sparing the region above the knees. The condition is also characterized by the presence of a supplementary row of eyelashes (distichiasis) that arise from glands in the upper and lower eyelids. Physical examination by a physician is typically necessary to identify this feature. This disorder has been linked to mutations in the gene known as FOXC2.

A third, more unusual, form of congenital lymphedema, hypotrichosis-lymphedema-telangiectasia, has been linked to mutations in the gene called  SOX18.

In addition to the above, a mutation of the CCBE1 has been identified in a very rare condition known as Hennekam's syndrome. This syndrome is characterized by the presence of lymphedema, lymphangiectasia (dilation of normally distributed lymphatic channels), mental retardation and unusual facial features.

It is very likely that the active efforts of geneticists and molecular biologists will continue to uncover additional genes that may be responsible for other forms of inherited lymphedema.