Lymphedema–distichiasis syndrome

Overview

Lymphedema–distichiasis syndrome (LDS) is a rare genetic disorder characterized by the presence of two primary features: lymphedema (chronic swelling, typically in the lower limbs) and distichiasis (a double row of eyelashes). Lymphedema usually appears around puberty or adolescence, while the extra eyelashes are present from birth. This syndrome can also be associated with other anomalies, such as heart defects, cleft palate, and abnormalities in the spinal cord or kidneys. Although it varies in severity, LDS is typically lifelong and requires multidisciplinary management.

Causes

Lymphedema–distichiasis syndrome is caused by mutations in the FOXC2 gene, which plays a key role in the development of the lymphatic and vascular systems. The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene inherited from either parent is sufficient to cause the disorder. The mutation disrupts normal lymphatic development, leading to fluid retention, and affects the development of the eyelids, resulting in extra eyelashes.

Symptoms

Symptoms of LDS vary in severity and can include:

• Lymphedema – typically affecting the lower limbs and appearing around puberty; may cause swelling, heaviness, and discomfort

• Distichiasis – presence of an extra row of eyelashes, often emerging from the Meibomian glands; may lead to irritation or corneal damage

• Eye symptoms – such as redness, watering, light sensitivity, or recurrent infections if the extra lashes scratch the eye

• Cardiovascular anomalies – including congenital heart defects or varicose veins

• Spinal or skeletal abnormalities – such as spina bifida or scoliosis in some individuals

• Cleft palate – reported in some cases

• Kidney malformations – in rare presentations

Diagnosis

Diagnosis of LDS is based on clinical findings and confirmed by genetic testing. Steps in the diagnostic process include:

• Physical examination – to assess for signs of lymphedema and abnormal eyelash growth

• Ophthalmologic evaluation – to detect distichiasis and assess its impact on eye health

• Lymphoscintigraphy or Doppler ultrasound – to evaluate lymphatic drainage in the limbs

• Genetic testing – to identify mutations in the FOXC2 gene and confirm the diagnosis

• Family history – assessment of related symptoms in other family members

Treatment

There is no cure for LDS, and treatment is aimed at managing symptoms and preventing complications. Management strategies include:

• Compression therapy – using compression garments or bandaging to reduce lymphedema and prevent fluid accumulation

• Manual lymphatic drainage (MLD) – specialized massage therapy to support lymph flow

• Hair removal or eyelash ablation – distichiasis may require electrolysis, cryotherapy, or laser removal to prevent eye irritation

• Lubricating eye drops or ointments – to soothe the eyes and prevent damage from abnormal lashes

• Ophthalmologic surgery – in severe cases of eye damage or chronic irritation

• Monitoring and treatment of associated anomalies – such as cardiac or renal issues

Prognosis

The prognosis for individuals with lymphedema–distichiasis syndrome is generally good with appropriate management. Lymphedema can be chronic and progressive if untreated, but regular care and compression therapy can improve function and quality of life. Eye complications from distichiasis are manageable, especially with early ophthalmologic intervention. Although associated anomalies may require specialized care, many individuals lead full and active lives with proper medical support and follow-up.