Milroy’s disease is a rare, inherited form of primary lymphedema, a disorder involving the lymphatic system. It is characterized by chronic swelling, or edema, most often present in the lower extremities, typically the feet and lower legs. This condition stems from a developmental abnormality in the lymphatic vessels, leading to the impaired drainage of lymph fluid. The fluid accumulates in the tissues, resulting in persistent swelling.
The Genetic Basis of Milroy’s Disease
Milroy’s disease is caused by a mutation in the FLT4 gene, located on chromosome 5. This gene provides instructions for making vascular endothelial growth factor receptor 3 (VEGFR-3), a protein instrumental in the formation and function of the lymphatic system.
The mutation disrupts the VEGFR-3 signaling pathway, leading to a failure in the development of a fully functional network of lymphatic vessels. Affected individuals are born with lymphatic vessels that are either too small, underdeveloped, or missing entirely (hypoplasia or aplasia). This structural deficiency prevents the lymphatic system from effectively transporting lymph fluid, causing it to pool in the lower limbs.
The disease follows an autosomal dominant inheritance pattern, meaning a person only needs one copy of the mutated FLT4 gene to have the condition. However, the severity of the swelling can vary widely, even among family members.
Identifying the Symptoms and Onset
The most noticeable symptom of Milroy’s disease is lymphedema, which is typically present at birth or develops shortly thereafter, often within the first year of life. This congenital onset is a defining feature of the condition. The edema primarily affects the feet and lower legs, often starting on the top of the foot and extending up toward the knee.
The swelling is frequently bilateral, affecting both legs, but it can be noticeably asymmetric. Initially, the edema may be “pitting,” where pressing the skin leaves a temporary indentation. Over time, the affected area becomes firmer and “non-pitting” due to the buildup of protein-rich fluid and subsequent skin changes, sometimes showing prominent veins or wart-like growths called papillomatosis.
Individuals with Milroy’s disease have an increased risk of cellulitis, a serious bacterial skin infection. Impaired lymphatic drainage compromises the local immune response, making the tissue vulnerable. Cellulitis episodes occur in about 20% of affected individuals and can further damage the compromised lymphatic vessels, increasing swelling and disease progression.
Diagnostic Procedures and Confirmation
Diagnosis usually begins with a thorough physical examination and a detailed medical history, focusing on the age of onset and family history of lower limb swelling. A physician looks for characteristic congenital or early-onset lymphedema confined to the lower extremities. Obtaining a family history is especially useful since the condition follows an autosomal dominant inheritance pattern.
Specialized imaging tests are often employed to confirm the diagnosis and rule out other causes of lymphedema. Lymphoscintigraphy is a common procedure where a radioactive tracer is injected into the web spaces of the toes. In Milroy’s disease, this test typically shows a lack of tracer uptake into the ilioinguinal lymph nodes, indicating poorly functioning or absent superficial lymphatic vessels, a finding referred to as “functional aplasia”.
The definitive confirmation involves molecular genetic testing. This testing analyzes the patient’s DNA to identify a pathogenic mutation in the FLT4 gene. While clinical presentation and imaging strongly suggest the diagnosis, identifying the specific genetic mutation provides certainty and is often the final step in the diagnostic process.
Treatment and Long-Term Management
Treatment focuses on managing symptoms and preventing complications, as Milroy’s disease is a chronic condition rooted in a structural defect. The primary intervention is Complete Decongestive Therapy (CDT), which is the standard of care for lymphedema management and has four main components:
- Manual lymphatic drainage (MLD): This is a specialized, gentle massage technique performed by a certified therapist to encourage the movement of accumulated fluid out of the swollen limb.
- Compression therapy: This involves the use of multi-layered bandaging followed by the long-term use of specialized compression garments or stockings. Compression applies external pressure to the limb, helping to reduce swelling and prevent fluid from re-accumulating.
- Meticulous skin care and hygiene: These are emphasized to reduce the risk of infection. Regular cleaning and moisturizing of the affected skin help maintain its integrity, which is important because minor cuts can become entry points for bacteria and trigger cellulitis.
- Remedial exercises and physical activity: These are encouraged, often performed while wearing compression garments, as muscle movement acts as a pump to improve lymph flow.
In individuals who experience frequent bouts of cellulitis, a physician may prescribe prophylactic antibiotics to minimize the risk of recurrent infections and limit further damage to the lymphatic system.