Milroy disease

Alternate names

Hereditary lymphedema; Congenital hereditary lymphedema; Early onset lymphedema; Hereditary lymphedema 1; Primary congenital lymphedema; Nonne-Milroy syndrome; Nonne-Milroy disease; Milroy's disease; Nonne’s syndrome; Congenital primary lymphedema; Hereditary lymphedema type I; Nonne-Milroy lymphedema

Summary

• Milroy disease is a condition that affects the normal function of the lymphatic system.
• The lymphatic system produces and transports fluids and immune cells throughout the body.
• Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema).
• Individuals with Milroy disease typically have lymphedema in their lower legs and feet at birth or develop it in infancy.
• The lymphedema typically occurs on both sides of the body and may worsen over time.

Epidemiology

The number of people with Milroy disease is not known. About 200 cases have been reported in the literature. Milroy disease occurs in all ethnic groups, and usually affects females more than males.

Cause

Mutations in the FLT4 gene cause some cases of Milroy disease. The FLT4 gene provides instructions for producing a protein called vascular endothelial growth factor receptor 3 (VEGFR-3), which regulates the development and maintenance of the lymphatic system. Mutations in the FLT4 gene interfere with the growth, movement, and survival of cells that line the lymphatic vessels (lymphatic endothelial cells). These mutations lead to the development of small or absent lymphatic vessels. If lymph fluid is not properly transported, it builds up in the body's tissues and causes lymphedema. It is not known how mutations in the FLT4 gene lead to the other features of this disorder.

Many individuals with Milroy disease do not have a mutation in the FLT4 gene. In these individuals, the cause of the disorder is unknown.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Milroy disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the FLT4 gene. These cases occur in people with no history of the disorder in their family. About 10 percent to 15 percent of people with a mutation in the FLT4 gene do not develop the features of Milroy disease.

Signs and symptoms

The following list includes the most common signs and symptoms in people with Milroy disease. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:

• Buildup of fluid (lymphedema) in the lower limbs
• Fluid buildup in the scrotum (hydrocele)
• Easily seen veins
• Upslanting toenails
• Wart-like growths (papillomatosis)
• Skin infection ([[cellulitis)
• Swelling of the lower limbs is usually present from before birth. It may gets worse over time, but in some cases lymphedema may improve. Skin changes may develop over the area of lymphedema, including thickened, scaly skin (hyperkeratosis) and wart-like growths (papillomatosis). People with Milroy disease may have an increased risk for developing serious skin infections and cancer.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Ankle swelling
• Cellulitis(Skin infection)
• Hydrocele testis
• Hyperkeratosis
• Pedal edema(Fluid accumulation in lower limbs)
• Predominantly lower limb lymphedema
• Toenail dysplasia(Abnormal toenail development)
• Varicose veins

5%-29% of people have these symptoms

• Angiosarcoma
• Behavioral abnormality(Behavioral changes)
• Epicanthus(Eye folds)
• Lichenification
• Neoplasm of the skin(Skin tumors)
• Specific learning disability

1%-4% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Erysipelas
• Hypoplasia of lymphatic vessels(Underdeveloped lymphatic vessels)
• Nonimmune hydrops fetalis
• Papilloma
• Prominent superficial veins(Prominent veins)
• Upslanting toenail
• Urethral stricture

Diagnosis

Milroy disease is diagnosed based on symptoms and clinical exam findings. Lymphoscintigraphy, a test done to check the lymphatic system for disease, can also be performed to help with the diagnosis. The diagnosis may be confirmed by molecular genetic testing of the FLT4 gene.

Treatment

Treatment of Milroy disease is focused on managing the symptoms. The lymphedema of the legs and feet may be controlled with the help of a lymphedema therapist, massage, compression stockings, or bandaging. If this management is ineffective then surgical treatment may be considered. Prevention of Secondary Complications Secondary cellulitis is prevented through the following measures:

• Prevention of foot infections, particularly athlete's foot/infected eczema
• Prompt treatment for early cellulitis with appropriate antibiotics. It may be necessary to give the first few doses intravenously.
• Prophylactic antibiotics in recurrent cases (e.g., penicillin V 500 mg daily)

NIH genetic and rare disease info

• NIH info on Milroy disease

Milroy disease is a rare disease.

Milroy disease Resources
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