Milroy's disease

Overview

Milroy’s disease, also known as primary congenital lymphedema, is a rare genetic disorder characterized by chronic swelling (lymphedema) that usually begins at or shortly after birth. The condition primarily affects the lower limbs, although other areas of the body may occasionally be involved. The swelling occurs due to improper development or dysfunction of the lymphatic vessels, which are responsible for draining lymph fluid from tissues back into the bloodstream.

Milroy’s disease is a form of primary lymphedema, meaning it arises from an intrinsic defect in the lymphatic system rather than as a result of surgery, infection, or trauma. The disorder is usually inherited in an autosomal dominant pattern and may affect multiple family members across generations. Although there is no cure, early diagnosis and appropriate management can help control symptoms and improve quality of life.

Causes

Milroy’s disease is caused by mutations in the FLT4 gene, which encodes a protein known as vascular endothelial growth factor receptor-3 (VEGFR-3). This receptor plays a crucial role in the development and maintenance of the lymphatic system, particularly in the formation of lymphatic vessels.

Mutations in the FLT4 gene disrupt normal signaling pathways needed for the growth and function of lymphatic vessels, resulting in poor drainage of lymph fluid and subsequent swelling. The disease follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. However, the condition can vary significantly in severity even within the same family.

Symptoms

The primary and most recognizable symptom of Milroy’s disease is lymphedema of the lower extremities, typically present from birth or early infancy. Symptoms can range from mild to severe and may include:

Primary Features

• Swelling (edema) of one or both feet and legs

• Pitting edema that may become non-pitting over time

• Thickened skin over affected areas

• Prominent veins on the legs

• Hardening or fibrosis of tissues in long-standing cases

Additional Features

• Upturned toenails or toenail abnormalities

• Warty outgrowths or papillomatosis of the skin

• Recurrent skin infections (cellulitis)

• Swelling of the scrotum in males

• Hydrocele (fluid accumulation in the scrotal sac)

The condition may worsen over time, especially if not managed properly. However, many affected individuals live normal lives with proper care and preventative measures.

Diagnosis

Diagnosis of Milroy’s disease is based on clinical evaluation, family history, and imaging studies. Genetic testing can confirm the diagnosis. Diagnostic approaches include:

• Clinical examination: Observing signs of congenital or early-onset lymphedema, especially in the lower limbs

• Family history: Assessing for a pattern of inherited swelling among family members

• Lymphoscintigraphy: A nuclear medicine test that visualizes lymphatic flow and identifies lymphatic vessel abnormalities

• Ultrasound: To evaluate soft tissue swelling and rule out other causes of edema

• Genetic testing: Identifying mutations in the FLT4 gene to confirm the diagnosis

Early and accurate diagnosis is essential for initiating appropriate management strategies to prevent complications and improve outcomes.

Treatment

There is no cure for Milroy’s disease, but treatment focuses on reducing swelling, preventing complications, and improving quality of life. Management typically involves a multidisciplinary approach and includes the following:

Conservative Management

• Compression therapy: Use of compression garments or bandages to promote lymphatic drainage

• Manual lymphatic drainage (MLD): A specialized massage technique performed by trained therapists

• Exercise: Regular, gentle exercise to improve lymph flow and maintain mobility

• Skin care: Preventing infections through meticulous hygiene and moisturizing

Medical and Surgical Options

• Antibiotics: Prompt treatment of skin infections such as cellulitis

• Diuretics: Generally not effective for lymphedema and not recommended long-term

• Surgery: Rarely used but may be considered in severe or refractory cases to reduce excess tissue or improve lymphatic drainage

Education on self-care, early signs of infection, and regular follow-up with healthcare providers is essential to minimize disease progression.

Prognosis

The prognosis for individuals with Milroy’s disease varies depending on the severity of the condition and the effectiveness of symptom management. While the condition is lifelong and progressive in some cases, many people can manage their symptoms successfully and lead full, active lives.

Key prognostic considerations include:

• Severity of lymphedema: Milder cases may remain stable for years, while more severe forms can lead to complications

• Risk of infections: Recurrent cellulitis can lead to worsening of symptoms and tissue damage

• Early intervention: Timely use of compression and therapy can significantly slow disease progression

Although Milroy’s disease has no cure, proactive management, patient education, and genetic counseling can help affected individuals maintain independence and prevent complications.