Lymphedema tarda
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Milroy's disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused by congenital abnormalities in the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
. Disruption of the normal drainage of lymph leads to fluid accumulation and hypertrophy of soft tissues. It was named by Sir William Osler for William Milroy, a Canadian physician, who described a case in 1892, though it was first described by Rudolf Virchow in 1863.


Presentation

The most common presentation of Milroy Disease is unilateral lower extremity lymphedema, and may also be accompanied by
hydrocele A hydrocele is an accumulation of serous fluid in a body cavity. A hydrocele testis, the most common form of hydrocele, is the accumulation of fluids around a testicle. It is often caused by fluid collecting within a layer wrapped around the testi ...
. Males and females may have upslanting toenails, deep creases in the toes, wart-like growths (papillomas), and prominent leg veins. Some individuals develop non-contagious skin infections called cellulitis that can damage the thin tubes that carry lymph fluid (lymphatic vessels). Episodes of cellulitis can cause further swelling in the lower limbs.


Genetics

This disease is more common in women and an association with the gene
FLT4 Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the ''FLT4'' gene. This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involve ...
has been described. FLT4 codes for
VEGFR-3 VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inhi ...
, which is implicated in development of the lymphatic system. Milroy's disease is also known as primary or hereditary lymphedema type 1A or early onset lymphedema. It is a very rare disease with only about 200 cases reported in the medical literature. Milroy's disease is an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
condition caused by a mutation in the
FLT4 Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the ''FLT4'' gene. This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involve ...
gene which encodes of the vascular endothelial growth factor receptor 3 (
VEGFR-3 VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inhi ...
) gene located on the long arm (q) on chromosome 5 (5q35.3). In contrast to Milroy's disease (early onset lymphedema type 1A,) which typically has its onset of swelling and edema at birth or during early infancy, hereditary lymphedema type II, known as
Meige disease Meige disease, or Meige lymphedema is a genetic disorder in which lymphedema later develops. Meige disease is a primary lymphedema that is not caused by another condition; secondary lymphedema is a typical consequence of a mastectomy. Another pr ...
, has its onset around the time of puberty. Meige disease is also an autosomal dominant disease. It has been linked to a mutations in the ‘forkhead’ family transcription factor (
FOXC2 Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the ''FOXC2'' gene. FOXC2 is a member of the ...
) gene located on the long arm of chromosome 16 (16q24.3). About 2000 cases have been identified. A third type of hereditary lymphedema, that has an onset after the age of 35 is known as lymph-edema tarda.


Diagnosis

Only conservative measures can be taken. Certain treatments for lymphedema disorders may possibly alleviate specific symptoms; no cure and it is usually congenital. Genetic counseling can be done. May have similar health conditions, delays, disorders, and physical traits associated with other lymphatic genetic diseases and chromosome #5 abnormalities.


Prognosis

MD does not normally affect life expectancy. Medscape states patients may have recurrent streptococcal cellulitis and lymphangitis, with subsequent hospitalizations for antibiotic therapy. A rare complication is the appearance of lymphangiosarcoma or angiosarcoma in patients with persistent lymphedema. Some patients may develop protein-losing enteropathy and visceral involvement. Chylous ascites and chylothorax rarely occur.


See also

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List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...


References


Further reading

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External links

{{DEFAULTSORT:Milroy's Disease Vascular-related cutaneous conditions Rare genetic syndromes