Learning About Milroy Disease: A Rare Inherited Form of Lymphedema

The lymphatic system is a body system responsible for draining fluid from the body’s tissues. Milroy disease is a genetic condition that usually runs in families. It is characterized by the lymphatic system failing in either one or both of the legs, which results in swelling. When the system fails, it does not drain and this is where the swelling comes from. The incidence of this condition is not known due to how rare this condition is.

Related Genes

This condition occurs due to a mutation in the FLT4 gene. This gene is responsible for giving the instructions necessary for the production of the vascular endothelial growth factor receptor 3 (VEGFR-3) protein. This protein is necessary for regulating the maintenance and development of the lymphatic system. When the FLT4 gene mutates, the mutation interferes with the movement, survival and growth of lymphatic cells. The mutations result in absent or small lymphatic vessels. If the lymphatic system cannot transport fluid properly, lymphedema develops due to fluid buildup in the tissues of the body. Whether or not FLT4 gene mutations cause the other symptoms of this condition is unknown. Many people with this condition do not have an FLT4 mutation. When this is the case, the cause of the condition is not known.

Inheritance Pattern

An autosomal dominant pattern is responsible for this condition. With this pattern, all that is required is a single copy of the mutated gene in each cell. Many people with this condition inherit the mutation from one of their affected parents. Other cases stem from a spontaneous FLT4 gene mutation. Approximately 10 to 15 percent of those with an FLT4 gene mutation will not go on to develop the features of this condition.

Symptoms and How this Condition Affects the Body

Under normal circumstances, the lymphatic system makes and sends immune cells and fluids throughout the body. With Milroy disease, the transport of these substances is abnormal and lymph fluid accumulates in the extremities. With this condition, the swelling is generally in the feet and legs shortly after birth. Both sides of the body are usually affected and over time the condition does not tend to get worse.

In addition to lymphedema, other features occur with this condition. Males may be born with urethra abnormalities or accumulation of fluid in their scrotums. Both genders may experience deep creases in their toes, prominent leg veins, upslanting toenails and wart-like growths. Cellulitis may also occur. Males are affected more often than females with cellulitis; this may cause the lower limbs to become more swollen.

Making the Diagnosis

Imaging studies may be done as part of the diagnostic process. Performing an ultrasound of the leg can be done to exclude other possible causes of the symptoms, such as vascular abnormalities like arteriovenous fistula.

Regular X-rays can be done to exclude bone abnormalities.

MRI, while more useful for lymph trunk anatomy, may be used. Lymphangiography with a subcutaneous dye injection and fluorescence microlymphography may also be helpful.

To look for an absence of lymphatic vessels, a doctor will order lymphoscintigraphy with the use of technetium-labeled colloid injected subcutaneously. A standard biopsy may also be done.

Treatments

The primary goal of treatment is to control the complications of the swollen limbs and to prevent infection. While there are no medications to treat this condition specifically, complications, such as bacteremia, cellulitis and chylothorax may be treated with medications as required. Benzopyrones, such as diosmin and coumarin, may help in stimulating proteolysis of proteins. Recurrent cellulitis may benefit from an antistreptococcal antibiotic. In low doses, benzathine penicillin or another type of prophylactic antibiotic therapy may be beneficial in preventing intermittent cellulitis.

To help with the lymphedema, elevating the affected leg, pneumatic compression or gentle massage, and elastic bandages or stockings may be beneficial. After the affected leg or foot has been given graded support, exercise should be encouraged as long as the patient is healthy enough. Along with elevation, exercise may help promote the movement of fluid away from the leg or foot.

A variety of surgical treatments have been tried, but none have been beneficial long-term.

Resources

Genetics Home Reference. (2008). Milroy Disease. Retrieved on June 11, 2011 from Genetics Home Reference

Kiel, R.J. MD et al. (2010). Milroy Disease. Retrieved on June 11, 2011 from eMedicine Medscape

Emory University. (2011). Single Gene Disorders and Milroy Disease. Retrieved on June 11, 2011 from Emory University