Lymphedema-distichiasis syndrome (LDS) is a rare, inherited disorder characterized by two primary features: lymphedema and distichiasis. Lymphedema involves swelling caused by a buildup of fluid, most often in the lower limbs, while distichiasis is the medical term for an extra row of eyelashes. Although the severity of symptoms can differ significantly among relatives, the onset of swelling often occurs in late childhood or around puberty.
The Genetic Cause of Lymphedema-Distichiasis Syndrome
Lymphedema-distichiasis syndrome is caused by mutations in the FOXC2 gene. This gene provides instructions for making a protein that acts as a transcription factor, which attaches to DNA and controls the activity of other genes. The FOXC2 protein is involved in the formation of many different tissues and organs during embryonic development.
The protein’s role is particularly important for the proper development of the lymphatic and vascular systems. The lymphatic system is a network of vessels that drains fluid from tissues and helps fight infection. Mutations in the FOXC2 gene disrupt these developmental processes.
This condition is inherited in an autosomal dominant pattern, meaning only one copy of the mutated FOXC2 gene from a parent is needed to cause the disorder. An affected parent has a 50% chance of passing the altered gene to each child. In some cases, the condition results from a new (de novo) mutation in a person with no family history of the disorder.
Primary Symptoms and Related Health Concerns
Lymphedema, the accumulation of lymph fluid in tissues, most commonly affects both legs and may also involve the external genitalia. The swelling can be asymmetrical, with one leg more affected than the other. Varicose veins are also a frequent finding and can develop even before the lymphedema becomes apparent.
Distichiasis is the growth of an extra row of eyelashes from the openings of the meibomian glands on the inner edge of the eyelid, and it is present from birth in most individuals. These aberrant eyelashes can cause significant eye irritation, recurrent conjunctivitis (pink eye), and light sensitivity (photophobia). In some cases, the lashes can scratch the cornea.
Beyond the primary symptoms, individuals with this syndrome may experience other health issues, including:
- Congenital heart defects
- A cleft palate (a gap in the roof of the mouth) or ptosis (drooping eyelids)
- Webbing of the neck
- Certain kidney anomalies
The Diagnostic Journey
The process of diagnosing lymphedema-distichiasis syndrome begins with a thorough clinical evaluation. A physician can suspect the syndrome based on the presence of lymphedema in the lower limbs and distichiasis. A family history of either lymphedema or distichiasis is also a strong indicator.
Molecular genetic testing is the standard approach for confirmation. This blood test analyzes the FOXC2 gene for a mutation, and identifying one confirms the diagnosis. This testing is also valuable for genetic counseling and family planning.
If genetic testing is unavailable or inconclusive, a diagnosis can be made on clinical grounds if both lymphedema and distichiasis are present. A newly diagnosed patient may also undergo an echocardiogram or renal ultrasound to screen for associated heart or kidney malformations.
Managing the Condition
Management of lymphedema-distichiasis syndrome focuses on addressing its specific symptoms, particularly the lymphedema and eye-related issues. For lymphedema, the standard approach is complete decongestive therapy (CDT), a program that includes manual lymphatic drainage. This is a type of specialized massage to move fluid out of the affected limbs.
This therapy is complemented by several other practices:
- Use of fitted compression garments or multi-layer bandaging to prevent fluid from reaccumulating.
- Meticulous skin care to keep the skin healthy and prevent infections like cellulitis.
- Specific exercises to aid lymphatic circulation.
- Avoidance of diuretic medications, which are not effective for this type of swelling.
For distichiasis, treatment depends on the severity of the symptoms. If the extra eyelashes are not causing problems, no intervention may be needed. For mild irritation, lubricating eye drops can provide relief. When the lashes cause pain, light sensitivity, or risk of corneal damage, more direct measures are taken, such as manual plucking (epilation), though this is a temporary solution.
More permanent options involve destroying the hair follicles through electrolysis or cryotherapy (freezing). In some cases, a surgical procedure to split the eyelid may be performed to address the abnormal lash growth. Any associated health concerns, like congenital heart defects, are managed by the appropriate specialists.