Posted by: patoconnor | October 29, 2008

Hereditary Lymphedema

HEREDITARY  LYMPHEDEMA 

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National Organization for Rare Disorders, Inc.

Lymphedema, Hereditary

Important

It is possible that the main title of the report is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms
None
Disorder Subdivisions
Hereditary Lymphedema, Type I
Congenital Hereditary Lymphedema
Milroy Disease
Nonne-Milroy-Meige Syndrome
Hereditary Lymphedema, Type II
Meige’s Lymphedema
Familial Lymphedema Praecox
Hereditary Lymphedema Tarda
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
Hereditary Angioedema
Lymphedema (Traumatic)
Elephantiasis
Distichiasis-Lymphedema Syndrome
Lymphedema and Ptosis

General Discussion

Hereditary Lymphedema is an inherited disorder of the lymphatic system that is characterized by abnormal swelling of certain parts of the body. The lymphatic system is a circulatory network of vessels, ducts, and nodes that filter and distribute certain fluid (lymph) and blood cells throughout the body. Lymphatic fluid collects in the soft tissues in and under the skin (subcutaneous) due to the 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. In most cases, Hereditary Lymphedema is inherited as an autosomal dominant genetic trait.

Symptoms

The primary symptom of Hereditary Lymphedema is swelling or puffiness in different parts of the body due to the accumulation of lymphatic fluid in the soft layers of tissue under the skin (lymphedema). Swelling frequently occurs below the waist, especially in the legs, but may also be present in the face, voice box (larynx), and arms. When lymphedema develops in the legs, swelling may begin in the foot and move upward. In some cases, swelling may cause discomfort and unusual tingling sensations (paresthesias) in the affected areas. Poor healing, following even minor trauma (e.g., cut or insect bite), may also occur; permanent structural changes in the skin, with abnormal thickening, often follow longstanding edema.

Infants with Hereditary Lymphedema Type I, also known as Congenital Hereditary Lymphedema or Milroy Disease, have areas of swelling at birth. The swelling tends to slowly worsen with advancing age.

Hereditary Lymphedema Type II or Meige Disease usually develops during childhood, adolescence, or early adulthood. This form of the disease usually produces severe swelling in areas below the waist. The first symptoms of Hereditary Lymphedema Type II usually include red skin over areas of swelling and associated discomfort and/or inflammation.

Hereditary Lymphedema Tarda usually occurs after the age of 35 years. The symptoms are similar to those of Hereditary Lymphedema Type II.

Complications of Hereditary Lymphedema may include inflammation of lymphatic vessels (lymphangitis) and infection of the skin (cellulitis) characterized by areas of warm and painful reddened skin that are hot to the touch. Red skin “streaks” may also develop. A general feeling of ill health (malaise), fever, chills, and/or headaches may also occur. If left untreated, cellulitis can lead to skin abscesses, areas of ulceration, and/or tissue damage (necrosis). Some people with this condition may develop persistent fluid accumulation in the lungs (pleural effusion). The most serious long-term complication of all forms of Hereditary Lymphedema is a minor increased risk for the development of a malignancy in the affected area (i.e., lymphangiosarcoma).

Causes

Most cases of Hereditary Lymphedema are inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

In some rare cases, Hereditary Lymphedema is thought to be inherited as an autosomal recessive or X-linked recessive genetic disorder.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.

Some cases of Hereditary Lymphedema may occur because of a spontaneous change in genetic material early in fetal development (sporadic).

The symptoms of Hereditary Lymphedema develop because of obstruction of the lymphatic vessels due to multiple malformations of the lymphatic vascular system. In some cases, there may be a reduction in the number of lymphatic vessels or the vessels may be underdeveloped (hypoplastic). However, in some cases, the reverse is true and lymphatic vessels may be unusually large (hyperplastic) and numerous.

Affected Populations

Congenital Hereditary Lymphedema (Type I) affects more females than males. Hereditary Lymphedema Type II (Meige Disease) affects males and females in equal numbers.

Approximately 1 in 6,000 people in the United States are affected by Hereditary Lymphedema. The symptoms of Congenital Hereditary Lymphedema (Type I) are typically present at birth. The onset of Hereditary Lymphedema Type II can occur during childhood, adolescence, or adulthood (i.e., between the ages of 10 to 35 years). The symptoms of Hereditary Lymphedema Tarda generally occur after the age of 35 years.

Related Disorders

Symptoms of the following disorders can be similar to those of Hereditary Lymphedema. Comparisons may be useful for a differential diagnosis:

Hereditary Angioedema is a rare inherited vascular disorder characterized by the excessive accumulation of body fluids in lymphatic vessels or veins. The outstanding symptom of this disorder is swelling (edema) on the back of the hands or feet, eyelids, lips, and/or genitals. Edema may also occur in the mucous membranes that line the respiratory and digestive tracts. The areas of swelling may be hard and painful, but they are typically not red or itchy (pruritic). A skin rash (urticaria) is rarely present. Hereditary Angioedema is inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose “Angioedema” as your search term in the Rare Disease Database.)

Traumatic Lymphedema is caused by injury to the lymph system or blunt trauma (bruising). Localized lymphedema may be due to postinfectious syndromes, post-radiation fibrosis, tumor growth, and/or surgery (e.g., mastectomy). Symptoms may include swelling, pitting, redness, discomfort, and/or tingling sensations.

Elephantiasis is an infectious tropical disease of the lymphatic system and is characterized by gross enlargement of an arm or leg or other areas of the trunk or head. The skin develops a thickened, pebbly appearance and may become ulcerated and darkened. Fever, chills, and a general feeling of ill health (malaise) may also be present. Inflammation of the lymphatic vessels causes extreme enlargement of the affected areas. This condition occurs most commonly in tropical regions and particularly in parts of Africa. (For more information on this disorder, choose “Elephantiasis” as your search term in the Rare Disease Database.)

The following disorders may occur in association with Hereditary Lymphedema as secondary characteristics. They are not necessary for a differential diagnosis:

Yellow Nail Syndrome is a rare disorder characterized by yellow, thickened, and curved nails with almost complete stoppage of nail growth. A loss of cuticles may also be associated with this syndrome. Loosening of the nails (onycholysis) may cause loss of some nails. This condition is usually associated with the presence of fluid in the lungs (plural effusion) and swelling of the arms and legs (lymphedema). Other respiratory problems may occur such as chronic inflammation of the bronchi and bronchioles (bronchiectasis), chronic bronchitis, and/or ongoing inflammation of the membranes that line the sinus cavities (sinusitis). The exact cause of this disease is not known. (For more information on this disorder, choose “Yellow Nail” as your search term in the Rare Disease Database.)

Distichiasis-Lymphedema Syndrome is a rare inherited disorder characterized by the presence of extra eyelashes (distichiasis) and swelling of the arms and legs (lymphedema). Swelling of the legs, especially below the knees, and eye irritation are common in people with this disorder. Occasionally, cysts on the spine (epidural) and other abnormalities of the spinal column may also occur. Distichiasis-Lymphedema Syndrome is inherited as an autosomal dominant genetic trait.

Lymphedema and Ptosis is an extremely rare inherited condition and is characterized by droopy eyelids (ptosis) and swelling (lymphedema), especially in the legs.

Standard Therapies

Diagnosis

The diagnosis of Hereditary Lymphedema may be confirmed by a thorough clinical evaluation and specialized imaging tests. The structure of the lymphatic system may be investigated with special nuclear studies (i.e., indirect radio isotope, lymphoscintigraphy, magnetic resonance imaging (MRI) or CT scanning may yield information that supports the diagnosis.

Treatment


Complete decongestive therapy (CDT) is a form of treatment in which specialized massage techniques are coupled with therapeutic bandaging, meticulous skin care, exercise, and the use of well-fitted compression garments.

Occasionally, drugs that promote excessive urinary output (i.e., diuretics) may be somewhat helpful for people with Hereditary Lymphedema. These medications increase urinary output and may help to reduce swelling in some affected individuals. However, diuretics have not been uniformly successful in reducing the swelling associated with this disorder. The prolonged use of diuretics for the treatment of Hereditary Lymphedema should be carefully directed by a physician as these medications may have several long-term side effects.

In some cases, the surgical joining of small lymphatic vessels to nearby small veins (microsurgical anastomosis) has had some limited success in people with Lymphedema. The goal of this surgery is to reduce swelling by creating new pathways for lymphatic fluid flow and “rechanneling” this flow into the venous system.

Genetic counseling will benefit people with Hereditary Lymphedema and their families.

Investigational Therapies

Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.


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