TYPES OF LYMPHEDEMA

TYPES OF LYMPHEDEMA

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TYPES OF PRIMARY LYMPHEDEMA

MILROY'S SYNDROME

Related Terms: Nonne-Milroy lymphedema, Milroy's Disease, Primary congenital hereditary lymphedema, hereditary lymphedema I, Nonne-Milroy-Meige disease

Milroy's Syndrome is an old term used to describe hereditary congenital lymphedema. It is a congenital familial primary lymphedema which results from vertical autosomal inheritance of a single gene. The gene has been identified as VEGFR3. The condition usually presents itself at birth with the swelling of one or even both legs.

If the condition is unilateral (single leg), the other leg may continue in the latency stage for years before expressing itself. The same is indicated for arm lymphedema.

It is the rarest of the inherited lymphedema, accounting for approximately 2% of hereditary lymphedemas.

Hereditary lymphedema was first described by Nonne in 1891, however in 1892 Dr. William F. Milroy described a missionary who had returned from work in India who had swollen legs his entire life. His mother likewise was afflicted with the same condition. Milroy had also, previously studied the 250 year history of a family and had been able to identify 22 persons with this condition through 6 generations. He was also able to pinpoint when the condition entered the family through a marriage in 1768.

Diagnosis

Basic diagnosis can be made by the fact that swelling (generally of the legs) presents at birth and there is a family history of similar swelling. Currently the most precise diagnosis can be made by a lymphoscintigraphy test. In this test a radioactive substance is injected into the limb and is traced on a computer screen. Through this method the exact location of the lymphatic blockages can be identified.

Etiology

The cause of Milroy's Syndrome is a break in the VEGFR3 gene.

Complications

The usual complications involved with the condition include fibrosis of the limb tissues, cellulitis (and or lymphangitis and erysipelas infections). Other complications made include involvement of the genitalia, pain, skin conditions and in very rare situations lymphangiosarcoma.

Treatment

Decongestive therapy is the most widely accepted form of treatment. There is no cure for Milroy's but the condition can be managed by early diagnosis and treatment.

Prognosis

Long term prognosis is excellent is the condition is identified early and treatment begins so after the diagnosis is made.

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MEIGE LYMPHEDEMA SYNDROME

See also: Nonne-Milroy-Meige Syndrome, Meige's lymphedema, Hereditary lymphedema II, familial lymphedema praecox

Form of primary hereditary lymphedema that starts at or around the time of puberty. The affected limbs are generally the legs.

Named after French physician Dr. Henri Meige who first described hereditary lymphedema in 1891. This form of lymphedema which usually presents itself at or during puberty is the most common of the hereditary lymphedemas, account for 65-80% of all diagnosed cases.

Meige-Type Lymphedema

Also known as Lymphedema II, this syndrome is similar to Lymphedema I but the onset of peripheral edema occurs during the second to the fifth decades. The legs are the most commonly involved, and lymphangiography reveals hypoplasia of peripheral lymphatics with dilation of lymphatic trunks.

Diagnosis

Basic diagnosis can be made by the fact that swelling (generally of the legs) presents during puberty and there is a family history of similar swelling. Currently the most precise diagnosis can be made by a lymphoscintigraphy test. In this test a radioactive substance is injected into the limb and is traced on a computer screen. Through this method the exact location of the lymphatic blockages can be identified.

Etiology

The cause of Lymphedema Praecox is a break in the VEGFR3 gene. The gene FOXC2 is implicated and there is also suspect third lymphedema gene.

Complications

Other Indications

Related conditions may also include yellow nail syndrome, pulmonary hypertension, cerebrovascular malformations and distichiasis

Treatment

Decongestive therapy is the most widely accepted form of treatment. There is no cure for Lymphedema praecox but the condition can be managed by early diagnosis and treatment.

Prognosis

Long term prognosis is excellent if the condition is identified early and treatment begins so after the diagnosis is made.

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LYMPHEDEMA TARDA

Form of primary hereditary lymphedema that expresses itself during middle age (generally onset 35+ years). Swelling generally occurs in the legs and may involve either one or both limbs. There is a higher incidence of lymphedema tarda among females than males.

This form of inherited lymphedema accounts for approximately 10% of those with primary lymphedema.

Diagnosis

Basic diagnosis can be made by the fact that swelling (generally of the legs) unexpectedly and there is a family history of similar swelling. Currently the most precise diagnosis can be made by a lymphoscintigraphy test. In this test a radioactive substance is injected into the limb and is traced on a computer screen. Through this method the exact location of the lymphatic blockages can be identified.

Etiology

The cause of lymphedema tarda is a break in the FOXC2 gene.

Complications

Treatment

Decongestive therapy is the most widely accepted form of treatment. There is no cure for lymphedema tarda but the condition can be managed by early diagnosis and treatment.

Prognosis

Long term prognosis is excellent is the condition is identified early and treatment begins so after the diagnosis is made.

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SECONDARY LYMPHEDEMA

SECONDARY LYMPHEDEMA is generally caused by an obstruction, damage to or injury to the lymph system that leads to an interruption of the normal lymphatic flow.

CAUSES

PRIMARY LYMPHEDEMA - The cause of hereditary primary lymphedema has been isolated to a malformation or break in two known genes. These are the FOXC2 and VEGFC genes. There is a suspected third gene, but as yet, it has not been identified. Causes of congenital primary lymphedema can be a developmental disorder of the lymphatics, in utero infection or injury and/or delivery difficulties.

SECONDARY LYMPHEDEMA - The causes of secondary lymphedema are multiple. Infections from insect bites, serious wounds, or burns can cause lymphedema when they damage or destroy lymphatics as kind any type of serious injury, radiation for cancer treatments is also a cause. Outside the tropics the number one cause of secondary lymphedema is the removal of lymph nodes for cancer biopsies. Hopefully, with the improved techniques of small needle biopsies, radiological diagnostic improvements and site specific node biopsies we will sees a marked decrease in this type of lymphedema.

In the tropical climates the most common cause of lymphedma is infection from filarial worms. Generally, resulting from mosquito bites. This parasite then grows eventually blocking and destroying the lymphatic system.

TREATMENT OPTIONS

The preferred treatment today is decongestive therapy. The forms of therapy are complete decongestive therapy (CDT) or manual decongestive therapy (MDT), there are variances, but most involve these two type of treatment.

Other treatments include the use of compression pumps, surgery, and newer approaches such as the use of lasers, liposuction, wholistic therapies and even acupuncture.

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LYMPHOEDEMA ASSOCIATION OF AUSTRALIA

What Are the Different Types of Primary Lymphoedema?

There are many different kinds of primary lymphoedema. Some are hereditary, but most are not. The list is far from complete. There are many syndromes which include lymphoedema, but they are rare syndromes. Listed below are a few of the identified syndromes.

Idiopathic Lymphoedema -Not Running in Families

This is the most common form of primary lymphoedema. As the name implies, this is primary lymphoedema of an unknown origin, and is not a part of a syndrome of other symptoms. It appears at birth or later on in an individual (more often female). Although it most commonly affects one lower extremity, it can affect any part of the body. It is not found in other family members because it is not hereditary and cannot be passed on to children. Lymphoscintigram findings will not show an obstruction as it would in acquired/secondary lymphoedema. Instead usually it will indicate a hypoplasia (underdevelopment of lymphatic vessels).

Primary Hereditary Lymphoedemas: Lymphoedemas Which Run in Families

Milroy’s Syndrome [also called Nonne-Milroy Syndrome]: Lymphoedema present at birth. Often the problem is a lack of initial lymphatics. [Autosomal Dominant,* chromosome 5]

Meige’s Syndrome : Like Milroy’s, but the lymphoedema does not appear until later: lymphoedema praecox (before 35) or lymphoedema tarda (after 35). [Autosomal Dominant]

Primary Hereditary Lymphoedemas with other symptoms

Yellow Nail Syndrome [Samman-White Syndrome]: Syndrome which includes discoloured thickened nails, pulmonary problems, and lymphoedema. Onset is usually childhood or early adulthood. [Autosomal Dominant]

Sharp-Aagenaes Syndrome: Distinguished by neonatal cholestasis (stoppage of bile excretion) with jaundice. The lymphoedema develops in early childhood and is equally seen in males and females. [Autosomal Recessive,* chromosome 15]

Lymphoedema with Distichiasis [Falls-Kertesz Syndrome]: As well as lymphoedema, there is an extra row of eyelashes (distichiasis); problems also include a widened spinal canal and other related problems. Onset is usually adolescence. [Autosomal Dominant, chromosome 16]

Avasthey-Roy Syndrome: As well as lymphoedema, there are arteriovenous malformations and pulmonary hypertension. Onset is usually adolescence. [Autosomal Dominant]

Hennekam’s Syndrome: Lymphoedema of face, genitals, and limbs; the face and nose are flat, the mouth narrow, the chin large, the ear malformed, the eyes protruding, the fingers can be webbed, the thumb large. There can be mild mental retardation. [Autosomal Recessive]

Noonan’s Syndrome: Includes webbed neck, protruding upper chest, receding lower chest, cardiomyopathy, short stature. Appears very similar to Turner’s Syndrome, below, except is not sex-linked.. [Autosomal dominant, chromosome 12]

Jeken’s Syndrome: Includes mental retardation, abnormal fat distribution at buttocks, and ataxia. Lymphoedema onset is during infancy. [Autosomal recessive, chromosome 16]

Figueroa Syndrome: Cleft palate; lymphoedema starts during childhood or adolescence. [Autosomal dominant]

Primary Lymphoedemas Associated with other Syndromes- Do Not Run In Families

Klippel-Trenaunay-[Weber] Syndrome: Venous and arterial alterations are present; when the lymph vessels are involved, they are frequently varicose. In Weber’s Syndrome, the bones of a limb are also hypertrophied (larger).[not hereditary]

Turner Syndrome: Affects only females because it is sex-linked.* Frequently the lymphatic system, (specifically the valves), is underdeveloped, resulting in childhood lymphoedema. This sometimes resolves by adolescence. Other features of Turner’s Syndrome include short stature, infertility, and sometimes problems with the heart, kidney, or thyroid.(XO instead of XX chromosome; not hereditary]

*Some Basic Genetics Terms:

Autosomal: a gene that is not on the sex-linked chromosome(x and y are the sex-linked chromosomes)

Dominant: only one of these genes must be present for the trait to exhibit itself

Recessive: the gene must be present from both parents for the trait to exhibit itself; a person with only one of the genes is said to be a carrier.

Incomplete penetrance: the situation when the dominant gene or two recessive genes are present, so the person should exhibit the trait, but in a certain percentage of cases, this does not happen

Ackowledgement

Lymphoedema Association of Australia

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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.

*Link no longer available*

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Advocates for Lymphedema

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Pat O'Connor

Lymphedema People / Advocates for Lymphedema

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For information about Lymphedema

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For Information about Lymphedema Complications

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For Lymphedema Personal Stories

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For information about Exercises for Lymphedema

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For information on Infections Associated with Lymphedema

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For information on Lymphedema in Children

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Lymphedema Glossary

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Lymphedema People - Support Groups

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Children with Lymphedema

The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People.

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Lipedema Lipodema Lipoedema

No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping.

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MEN WITH LYMPHEDEMA

If you are a man with lymphedema; a man with a loved one with lymphedema who you are trying to help and understand come join us and discover what it is to be the master instead of the sufferer of lymphedema.

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All About Lymphangiectasia

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

http://health.groups.yahoo.com/group/allaboutlymphangiectasia/

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Lymphatic Disorders Support Group @ Yahoo Groups

While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.

DISCRIPTION

Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People.

http://health.groups.yahoo.com/group/lymphaticdisorders/

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All About Lymphedema

For our Google fans, we have just created this online support group in Google Groups:

Homepage: http://groups-beta.google.com/group/All-About-Lymphedema

Group email: All-About-Lymphedema@googlegroups.com

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Lymphedema Friends

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If you an AOL fan and looking for a support group in AOL Groups, come and join us there.

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Lymphedema People New Wiki Pages

Have you seen our new “Wiki” pages yet? Listed below are just a sample of the more than 140 pages now listed in our Wiki section. We are also working on hundred more. Come and take a stroll!

Lymphedema Glossary

http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing

Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema

Arm Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=arm_lymphedema

Leg Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=leg_lymphedema

Acute Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=acute_lymphedema

The Lymphedema Diet

http://www.lymphedemapeople.com/wiki/doku.php?id=the_lymphedema_diet