About lymphedema hereditary

What is lymphedema hereditary?

Hereditary lymphedema is a genetic developmental disorder affecting the lymphatic system. It is characterized by swelling (edema) of certain parts of the body. The lymphatic system is a circulatory network of vessels, ducts, and nodes that filter and distribute certain protein-rich fluid (lymph) and blood cells throughout the body. In hereditary lymphedema, lymphatic fluid collects in the subcutaneous tissues under the epidermis due to obstruction, malformation, or underdevelopment (hypoplasia) of various lymphatic vessels. There are three forms of hereditary lymphedema: congenital hereditary lymphedema or Milroy disease; lymphedema praecox or Meige disease; and lymphedema tarda. Symptoms include swelling (lymphedema) and thickening and hardening of the skin in affected areas. In most cases, hereditary lymphedema is inherited as an autosomal dominant trait.

Lymphedema may be classified as primary or secondary. Hereditary lymphedema is also known as primary lymphedema. Secondary lymphedema occurs because of damage to the lymphatic system from surgery, radiation therapy, trauma or infection (e.g. filariasis).

Lipedema is a symmetrical accumulation of subcutaneous fat, most often in the legs. Lipedema occurs almost exclusively in females. Tenderness and bruising are alsocommon. Lipedema is frequently misdiagnosed as lymphedema.

What are the symptoms for lymphedema hereditary?

The main symptom associated with hereditary lymphedema is edema in different parts of the body due to accumulation of lymph in the soft layers of tissue under the epidermis. Swelling frequently occurs in one or both legs, but may also be present in the trunk, face, genitalia and arms. When lymphedema develops in the legs, swelling is usually most noticeable in the foot and ankle but may also be present in the calf and thigh. In some people, swelling may cause tightness, discomfort and unusual tingling sensations (paresthesias) in the affected areas. The affected area heals poorly even after minor trauma (e.g., cut or insect bite). The skin of the affected area may become abnormally dry, thickened or scaly skin (hyperkeratosis) resulting in a “woody” texture.

Hereditary lymphedema type I (Milroy disease) is characterized by edema that is present at or shortly after birth (congenital). Ultrasound scanning during pregnancy may indicate if a fetus is affected if swelling of the dorsum of the feet is noted in the second or third trimester. In rare cases, edema may develop later in life. The legs are most often affected, and in some patients, the genitals may also be affected. The extent and location of edema varies greatly from person to person even among individuals in the same family. Additional complications sometimes associated with hereditary lymphedema type I include upslanting toenails, small warty growths on the affected areas (papillomatosis), abnormally large or prominent veins below the knees and in males, urethral abnormalities and the development of a fluid-filled sac along the spermatic cord of the scrotum (hydrocele). Bacterial infection of the skin and underlying soft tissues (cellulitis) has also been reported in approximately 20% of individuals, which may increase swelling due to additional damage to lymphatic vessels.

Hereditary lymphedema type II (Meige disease or lymphedema praecox) develops around puberty or shortly thereafter in most individuals. This is the most common type of primary lymphedema. In addition to lymphedema of the legs, other areas of the body such as the arms, face and voice box (larynx) may be affected. Some individuals may develop yellow nails.

Lymphedema tarda is defined as primary lymphedema occurring after the age of 35. Edema primarily occurs in the legs, but the arms and other areas may be affected as well. In women, the lower extremities are most often affected.

In all subtypes of hereditary lymphedema, the degree of edema can progress; in some people, especially in early years, edema may improve over time. Obesity makes management of lymphedema more difficult. Affected individuals with lymphedema are at risk for developing infections including cellulitis or infection of the lymphatic vessels (lymphangitis). These infections are characterized by areas of warm, painful and reddened skin. Red skin “streaks” may also develop in the infected area. Increased edema is common. A general feeling of ill health (malaise), fever, chills and/or Headaches may also occur. If left untreated, cellulitis can lead to septicemia, skin abscesses, areas of ulceration and/or tissue damage (necrosis). Cellulitis is more common in males than females. Athlete’s foot (tinea pedis) can cause cracks in the interdigital skin, bacterial invasion and cellulitis. Pregnant individuals with hereditary lymphedema may experience increased swelling during pregnancy.

In rare cases, additional complications can include accumulation of milky fluid consisting of fat droplets and lymph (chyle). Chyle is absorbed during digestion by the lymphatic vessels located around the intestine and drains into the thoracic duct in the upper chest before being deposited into veins, where it mixes with blood. In some individuals with hereditary lymphedema, the lymphatic vessels may rupture or become blocked (obstructed), causing chyle to accumulate in the chest cavity (chylothorax) or abdomen (chylous ascites).

Affected individuals may also be at a greater risk than the general population for developing a malignancy at the affected site. These malignancies include angiosarcoma, which are cancerous tumors that develop from blood or lymphatic vessels. They may occur in any area of the body. A specific type of angiosarComa is known as lymphangiosarcoma, or Stewart-Treves syndrome. Rarely, this cancerous tumor may develop in long-standing cases of primary or secondary lymphedema. AngiosarComa occurs in the lymphedematous extremity but can spread to the adjacent trunk and lungs.

What are the causes for lymphedema hereditary?

Most cases of hereditary lymphedema type I are caused by changes (mutations) in the FMS-like tyrosine kinase 4 (FLT4) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body. The FLT4 gene provides instructions to make a protein called vascular endothelial growth factor receptor 3 (VEGFR-3) that regulates the development and maintenance of the lymphatic system. Some cases of hereditary lymphedema type II and lymphedema tarda have been linked to mutations in the forkhead box C2 (FOXC2) gene, which plays an essential role in regulating lymphatic valve development. Mutations in these genes cause abnormalities in the lymphatic system that do not allow fluid to drain properly, resulting in edema.

Most cases of hereditary lymphedema type I and type II are inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

Most individuals diagnosed with hereditary lymphedema type I have an affected parent, though approximately 10% may have the disorder due to a non-inherited (de novo) FLT4 mutation. Approximately 85%-90% of individuals with a FLT4 mutation will develop edema in the lower extremities by 3 years of age, while 10%-15% will show no signs or symptoms of lymphedema (reduced penetrance). Types and severity of symptoms can vary widely even within the same family (variable expressivity).

What are the treatments for lymphedema hereditary?

Treatment for hereditary lymphedema focuses on management of symptoms, primarily reducing edema and preventing infection. For lower leg edema, referral to a lymphedema therapist is recommended. Treatment approaches may include fitting compression hosiery and/or bandaging, massage, supportive shoes, and good skin care. Complete decongestive therapy (CDT) is a form of treatment in which specialized manual techniques (manual lymph drainage) is combined with multi-layered compression bandaging, meticulous skin care, exercise, and the use of well-fitted compression garments. Rehabilitation therapy may be necessary in cases where extreme lymphedema impairs daily activities.

Various surgical techniques have been used to treat individuals with hereditary lymphedema, including the joining of small lymphatic vessels to nearby small veins (microsurgical anastomosis) with the goal of creating new pathways to “rechannel” lymphatic fluid flow into the venous system and thereby reduce swelling. However, this surgery is not generally recommended as limited effectiveness has been reported in the medical literature. Surgery to remove excess fibrous tissue (reducing operation) for cases of severe lymphedema is also available but continued use of compression garments is still necessary. Removal of fat from under the skin (liposuction) has not been found to be effective in primary lymphedema.

To prevent progression of edema or infection, individuals with hereditary lymphedema should avoid long periods of immobility with their legs placed in a downward position at a level lower than the heart (dependent position) and reduce excessive salt intake to decrease fluid retention. Special care should be taken to avoid wounds in any affected area due to reduced resistance to infection. Certain medications such as calcium channel blocking drugs and non-steroidal anti-inflammatory drugs (NSAIDs) may worsen edema in the legs and the benefits and risks of using these medications should be thoroughly discussed with the patient’s physician.

Antibiotics can be used to treat infections such as cellulitis or as a preventive (prophylactic) measure for recurrent infections and athlete’s foot can be treated with antifungal topical medications. Individuals with primary chylous ascites complications should follow a no-fat diet supplemented with medium chain triglycerides and vitamins. Addition of a diuretic such as spironolactone has been reported to be a valuable adjunct to dietary control.

There are currently no available gene therapies or medications approved by the U.S. Food and Drug Administration (FDA) to treat hereditary lymphedema.

Genetic counseling and testing may benefit individuals with hereditary lymphedema and their families.

What are the risk factors for lymphedema hereditary?

Hereditary lymphedema affects females more often than males and is one of the most common causes of primary lymphedema. The estimated prevalence of these disorders is 1 in 6,000 – 10,000 individuals in the general population, and it occurs in all ethnic groups. Hereditary lymphedema type II (Meige syndrome) is the most common form accounting for approximately 80 percent of cases. The prevalence of hereditary lymphedema type I (Milroy disease) is unknown. Approximately 200 cases have been reported in the medical literature.

Is there a cure/medications for lymphedema hereditary?

Cure/medications for lymphedema hereditary:
1. Hereditary lymphedema treatment focuses on symptom management, especially lowering edema and avoiding infection. Referral to a lymphedema therapist is advised for lower leg edema.
2. Fitting compression hosiery, bandaging, massage, supportive footwear, and proper skin care are all possible treatment options.
3. Complete decongestive therapy (CDT) is a type of care that combines specialist manual procedures (manual lymph drainage) with many layers of compression bandaging, attentive skin care, exercise, and the use of compression clothing that is properly sized for the patient.
4. In situations when severe lymphedema makes daily tasks difficult, rehabilitation therapy may be required.
5. Hereditary lymphedema patients have received treatment using a variety of surgical procedures, such as microsurgical anastomosis, which involves uniting neighboring small veins and small lymphatic vessels to "rechannel" lymphatic fluid flow and lessen swelling.
6. However, due to the minimal effect that has been noted in the medical literature, this surgery is generally not advised.
7. In cases of severe lymphedema, surgery to remove extra fibrous tissue (reduction operation) is also an option, but compression clothing must still be worn continuously.
8. Liposuction, which removes fat beneath the skin, has not been demonstrated to be beneficial in treating primary lymphedema.
9. There are no gene treatments or medicines on the market right now that have been approved to treat hereditary lymphedema.
10. Families and individuals with hereditary lymphedema may benefit from genetic counseling and testing.

Swelling of the entire or just a portion of the arm, leg, fingers, or toes,A sensation of tightness,Limitation of movement,Persistent infections
Fibrosis( Skin that is hardening and becoming thicker)

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