Lymphedema-distichiasis syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Lymphedema-distichiasis syndrome is a condition that affects the normal function of the lymphatic system, which is a part of the circulatory and immune systems. The lymphatic system produces and transports fluids and immune cells throughout the body. 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).

All people with lymphedema-distichiasis syndrome have extra eyelashes present at birth. 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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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 and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Conjunctivitis · Very frequent (99-80%)

Inflammation of the conjunctiva.

Corneal erosion · Very frequent (99-80%)

An erosion or abrasion of the cornea's outermost layer of epithelial cells.

Distichiasis · Very frequent (99-80%)

Double rows of eyelashes.

Photophobia · Very frequent (99-80%)

Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.

Predominantly lower limb lymphedema · Very frequent (99-80%)

Localized fluid retention and tissue swelling caused by a compromised lymphatic system, affecting mainly the legs.

Cataract · Frequent (79-30%)

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Ectropion · Frequent (79-30%)

An outward turning (eversion) or rotation of the eyelid margin.

Muscle weakness · Frequent (79-30%)

Reduced strength of muscles.

Ptosis · Frequent (79-30%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Varicose veins · Frequent (79-30%)

Enlarged and tortuous veins.

Abnormal cardiovascular system morphology · Occasional (29-5%)

Any structural anomaly of the heart and blood vessels.

Arrhythmia · Occasional (29-5%)

Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.

Cleft palate · Occasional (29-5%)

Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Cleft upper lip · Occasional (29-5%)

A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.

Other findings in the same source

From: Orphanet

Additional reported features include Diabetes mellitus (Occasional (29-5%)); Fibrosarcoma (Occasional (29-5%)); Glomerulopathy (Occasional (29-5%)); Patent ductus arteriosus (Occasional (29-5%)); Proteinuria (Occasional (29-5%)); Recurrent skin infections (Occasional (29-5%)); Recurrent urinary tract infections (Occasional (29-5%)); Renal duplication (Occasional (29-5%)); Spinalarachnoid cyst (Occasional (29-5%)); Tubulointerstitial nephritis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Lymphedema-distichiasis syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

Additional services that may be relevant, depending on the findings, include: Vascular Medicine.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Lymphedema-distichiasis syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.