Lymphedema-distichiasis syndrome (LDS) is a rare genetic condition that affects the lymphatic system and eyelash development. It is defined by its two hallmark features, which give the condition its name:

1. Lymphedema: This is a type of chronic swelling that occurs when lymphatic fluid accumulates in the soft tissues of the body. The lymphatic system is a crucial part of our circulatory and immune systems. To understand it, it is helpful to use an analogy. Think of your lymphatic system as a network of tiny drainage pipes running alongside your blood vessels. Their job is to collect excess fluid, waste products, and proteins from your tissues and return this fluid to the bloodstream. In the lymphedema component of LDS, the “drainage pipes” in the legs were not constructed correctly during development. They may be too narrow, underdeveloped, or have faulty valves. This structural problem prevents the lymphatic fluid from draining properly, causing it to back up and pool in the tissues, leading to persistent swelling.
2. Distichiasis: This is the medical term for the abnormal growth of an extra row of eyelashes. In a typical eyelid, eyelashes grow only from the outer front edge. In individuals with distichiasis, a partial or complete second row of lashes emerges from the openings of the meibomian glands, which are the tiny oil glands located on the inner margin of the eyelid right behind the normal lashes.

While this combination of leg swelling and extra eyelashes defines the syndrome, LDS is a spectrum disorder. Symptom severity can vary widely, even among members of the same family. Some individuals may have significant lymphedema with only minor eye findings, while others may have troublesome eyelashes with very mild swelling.

In my experience, LDS often goes unnoticed until adolescence or early adulthood when leg swelling begins or eye irritation from extra eyelashes becomes hard to ignore. It’s a diagnosis that requires a careful look at seemingly unrelated symptoms.

Lymphedema-Distichiasis Syndrome is caused by a mutation in the FOXC2 gene. This gene is located on chromosome 16 and belongs to a family of “transcription factor” genes. Transcription factors are like master-level foremen on a construction site; they control the activity of many other genes, turning them on or off at critical times during embryonic development.

The FOXC2 gene plays a vital role in orchestrating the proper formation of several different body systems, most notably the lymphatic vessels and the valves within both lymphatic vessels and veins. It also has a role in the development of the eyes and skeleton.

When the FOXC2 gene is mutated, the protein it produces is faulty. This disrupts the normal developmental signals, leading to the malformation of the lymphatic vessels, which causes lymphedema, and the abnormal development of the eyelid glands, which results in distichiasis. This single genetic cause explains why these two seemingly unrelated problems occur together in this specific syndrome (National Organization for Rare Disorders [NORD], 2023).

Genetic testing makes a huge difference in such conditions. I’ve worked with families where the swelling and eye symptoms were treated separately for years before someone connected the dots and tested for FOXC2 mutations.

Lymphedema-Distichiasis Syndrome is an inherited genetic disorder. In most cases, it is passed down through families in an autosomal dominant pattern.

• Autosomal dominant means that an individual only needs to inherit one copy of the mutated FOXC2 gene from one parent to have the syndrome.
• An affected parent who has the condition has a 50% chance of passing the mutated gene, and thus the syndrome, on to each of their children, regardless of the child’s gender.

LDS is known for having variable expressivity. This is a critical concept for families to understand. It means that even though family members may share the exact same gene mutation, the way the syndrome affects them can be very different. One parent might have severe lymphedema, while their child has only very mild, barely noticeable swelling but significant eye irritation from distichiasis.

In some cases, the condition can also occur due to a de novo (new) mutation. This means the mutation in the FOXC2 gene occurs spontaneously in an individual for the first time, with no prior family history of the disorder.

In families with a known mutation, I always recommend genetic counseling especially when a child starts showing even mild swelling or frequent eye discomfort. Early awareness can help manage symptoms more effectively.

Symptoms typically appear in late childhood or adolescence, though they can vary in severity. The two hallmark features are lymphedema and distichiasis.

Lymphedema

• This is the syndrome’s most common feature. The swelling typically affects both legs (bilateral), starting at the feet and extending up to the knees.
• The onset is a key characteristic: the lymphedema is not usually present at birth but typically develops around the time of puberty or in early adulthood.
• The swelling is a type of pitting edema. This means that if you press a finger firmly into the swollen area for a few seconds, it will leave an indent.
• The legs may feel heavy, achy, and uncomfortable.
• Over time, chronic lymphedema can lead to thickening and hardening of the skin.
• A major risk associated with lymphedema is a recurrent bacterial skin infection called cellulitis.

Distichiasis (Double Eyelashes)

• This feature is present from birth.
• There is a partial or complete extra row of eyelashes that are often thinner and shorter than the normal lashes and emerge from the inner rim of the eyelid.
• For many people, the extra lashes are soft and cause no problems.
• For others, they can be stiff and may rub against the surface of the eye (the cornea), causing:
  • Eye irritation and a feeling of having something in the eye.
  • Increased tearing.
  • Redness.
  • Sensitivity to light (photophobia).
  • In some cases, corneal abrasions (scratches) or scarring.

Other Associated Symptoms

While less common than lymphedema and distichiasis, individuals with LDS have a higher incidence of several other medical issues. These can include:

• Varicose veins that appear at an unusually young age.
• Congenital heart defects, such as a VSD or Tetralogy of Fallot.
• Cleft palate, sometimes with or without a cleft lip.
• Ptosis (drooping of the upper eyelids).
• Spinal cysts (Tarlov cysts), which are fluid-filled sacs on the nerve roots of the spine that can sometimes cause pain or neurological symptoms.

I’ve seen patients go years thinking their leg swelling was from standing too long or that their eye irritation was just allergies. When you put the two together, persistent leg swelling and double eyelashes, the diagnosis becomes clearer.

The diagnosis of Lymphedema-Distichiasis Syndrome is based on clinical signs, family history, and genetic testing.

The diagnostic process involves a thorough evaluation by several specialists:

1. Clinical Examination: A detailed physical exam is performed to assess the characteristic pitting edema in the legs. An ophthalmologist (eye doctor) must perform a slit-lamp examination to carefully inspect the eyelids and confirm the presence of the abnormal second row of eyelashes.
2. Family History: A doctor will take a comprehensive family history to look for other members who may have had leg swelling or recurrent eye irritation, as the condition is often inherited.
3. Screening for Associated Conditions: Because of the known associations, a new diagnosis of LDS should prompt a full medical workup. This includes an echocardiogram of the heart and sometimes imaging of the spine.
4. Lymphoscintigraphy: A specialized imaging test that can visualize the lymphatic system and confirm impaired drainage.
5. Genetic Testing: The diagnosis can be definitively confirmed through molecular genetic testing. A blood test can be done to sequence the FOXC2 gene and identify the causative mutation. This is valuable for confirming the diagnosis, for genetic counseling, and for making informed family planning decisions (NIH Genetic and Rare Diseases Information Center [GARD], 2023).

I always look beyond the obvious. When a patient presents with “just” leg swelling or “just” eye discomfort, asking about family history or digging deeper with imaging can lead to a breakthrough diagnosis.

There is no cure for the underlying genetic defect in Lymphedema-Distichiasis Syndrome but symptoms can be managed with a multidisciplinary approach.

1. Managing Lymphedema

This is the cornerstone of management and requires diligent self-care. The gold standard of care is Complete Decongestive Therapy (CDT), which has two phases:

• Intensive Phase: This is performed by a certified lymphedema therapist. It involves daily sessions of Manual Lymphatic Drainage (MLD), a specialized, gentle massage technique to manually re-route lymphatic fluid, followed by multi-layer compression bandaging to reduce the swelling.
• Maintenance Phase: This is the lifelong, daily self-care program that the patient performs at home. It includes:
  • Wearing custom-fitted medical-grade compression garments (like stockings or tights) every day to prevent fluid from re-accumulating.
  • Meticulous skin care, keeping the skin clean and well-moisturized to prevent cracks that can lead to infection.
  • A program of gentle exercise, which helps the muscle pump action move lymphatic fluid.
  • Maintaining a healthy weight.

The most important part of lymphedema management is preventing cellulitis, a serious bacterial skin infection. Any cut, scrape, or insect bite on the affected legs must be cleaned immediately and treated with an antiseptic.

2. Managing Distichiasis

• If the extra lashes are soft and cause no symptoms, no treatment is needed.
• If they are causing eye irritation, the first step is often the use of lubricating eye drops and ointments.
• For more persistent irritation, an ophthalmologist may recommend procedures to remove the problematic lashes. This can include:
  • Epilation: Regular plucking of the lashes, though they will grow back.
  • Electrolysis or Cryotherapy: Procedures that use electricity or freezing to permanently destroy the abnormal hair follicles.

3. Managing Associated Conditions

Any associated heart defects or other medical issues are managed by the appropriate specialists, such as a cardiologist or an orthopedic surgeon.

What makes LDS manageable is having the right team, an eye doctor, lymphatic therapist, and genetic counselor. Coordinated care prevents complications and helps patients maintain daily comfort.

Lymphedema-Distichiasis Syndrome is a rare genetic disorder that presents a unique combination of symptoms affecting the lymphatic system and the eyes. While the diagnosis can be daunting, understanding that these disparate features all stem from a single faulty gene is the key to a comprehensive approach to care. There is no cure for LDS, but its most impactful symptom lymphedema can be managed very effectively with diligent, consistent therapy, primarily involving compression garments and meticulous skin care. For those affected by the condition, a correct diagnosis unlocks a pathway to the right treatments and empowers them to take control of their health. I always tell families that while LDS is lifelong, it doesn’t have to be limiting. With the right support and consistent care, most people can lead full and active lives.

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2023). Lymphedema-distichiasis syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/6950/lymphedema-distichiasis-syndrome

National Organization for Rare Disorders (NORD). (2023). Lymphedema-Distichiasis Syndrome. Retrieved from https://rarediseases.org/rare-diseases/lymphedema-distichiasis-syndrome/