Lymphedema–distichiasis syndrome

Alternate names

Lymphedema with distichiasis; Hereditary lymphedema-distichiasis syndrome (subtype)

Definition

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).

Summary

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.

Epidemiology

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.

Cause

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).

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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.

Signs and symptoms

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). For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Conjunctivitis(Pink eye)
• Corneal erosion(Damage to outer layer of the cornea of the eye)
• Distichiasis
• Photophobia(Extreme sensitivity of the eyes to light)
• Predominantly lower limb lymphedema

30%-79% of people have these symptoms

• Cataract(Clouding of the lens of the eye)
• Ectropion(Eyelid turned out)
• Muscle weakness(Muscular weakness)
• Ptosis(Drooping upper eyelid)
• Varicose veins

5%-29% of people have these symptoms

• Abnormality of the pulmonary vasculature(Abnormality of the lung blood vessels)
• Arrhythmia(Abnormal heart rate)
• Cleft palate(Cleft roof of mouth)
• Cleft upper lip(Harelip)
• Diabetes mellitus
• Fibrosarcoma
• Glomerulopathy
• Patent ductus arteriosus
• Proteinuria(High urine protein levels)
• Recurrent skin infections(Skin infections, recurrent)
• Recurrent urinary tract infections(Frequent urinary tract infections)
• Renal duplication(Extra kidney)
• Spinalarachnoid cyst
• Tubulointerstitial nephritis
• Webbed neck(Neck webbing)

1%-4% of people have these symptoms

• Yellow nails

Diagnosis

Currently, the most accurate test to determine if an individual is affected by lymphedema-distichiasis syndrome is done via Sanger sequencing, which includes whole genome analysis and single gene and multigene testing. Sequenced DNA that exhibits mutations in the FOXC2 gene are considered confirmed clinical diagnoses. In addition to Sanger sequencing, Multiplex Ligation Probe Amplification (MLPA) can be used to determine if duplications and deletions in FOXC2 are present in an individual, making it a practical testing mechanism. Lastly, diagnosis is sometimes determined without genome testing. If an individual exhibits multiple symptoms of lymphedema-distichiasis and has a medical history consistent with known lymphedema-distichiasis symptoms, then their diagnosis is confirmed via clinical evaluation.

Treatment

Treatment is directed at the specific symptoms present in each case. This may include complete decongestive therapy, a comprehensive management technique used to treat lympedema and/or lubrication and removal of the extra eyelashes via plucking, cryotherapy, or electrolysis.

NIH genetic and rare disease info

• NIH info on Lymphedema–distichiasis syndrome

Lymphedema–distichiasis syndrome is a rare disease.

Lymphedema–distichiasis syndrome Resources
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