Milroy disease
Milroy disease is a rare genetic disorder that impairs the lymphatic system, causing congenital swelling in the lower limbs and feet due to the accumulation of lymph fluid.
Overview
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.
Symptoms & Clinical Features
Milroy disease is associated with other features in addition to lymphedema. These can include:
- An accumulation of fluid in the scrotum (hydrocele) in newborn males
- Upslanting toenails
- Deep creases in the toes
- Wart-like growths (papillomas)
- Prominent leg veins
- Episodes of non-contagious skin infections called cellulitis, which can damage the thin tubes that carry lymph fluid (**lymphatic vessels**) and cause further swelling in the lower limbs
Frequency
Milroy disease is a rare disorder; its precise incidence is unknown.
Causes
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 currently 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 Pattern
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 an affected parent. Other cases may result from new mutations in the FLT4 gene, occurring 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.
Other Names for This Condition
- Congenital familial lymphedema
- Hereditary lymphedema type I
- Milroy's disease
- Nonne-Milroy lymphedema