Lymphedema-distichiasis syndrome

Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system (part of the immune system that produces and transports fluids and immune cells throughout the body). People with this condition 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. The abnormal eyelashes can cause damage to the clear covering of the eye (cornea) because the lashes often touch the eyeball. 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; however, the age of onset of lymphedema varies. Males usually develop lymphedema earlier than females, but all those affected will develop lymphedema by the time they are in their forties.

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

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).

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.