HEREDITARY PRIMARY LYMPHEDEMA
-------------------------------------------------------------
Lymphedema, Hereditary
Lymphedema
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)
Lymphatic
Filariasis
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), neck
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 (fibrosis),
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*
References
ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). Victor A. McKusick, Editor;
Johns
Hopkins University, last edit date 4/18/95. Entry Number 153200; last
edit date
3/9/99, Entry Number 153100; last edit date 11/6/94, Entry Number
153000.
CECIL TEXTBOOK OF MEDICINE, 20th Ed.: J. Claude Bennett and Fred Plum,
Editors;
W.B. Saunders Co., 1996. P. 357.
HARRISON'S PRINCIPLES OF INTERNAL MEDICINE, 14th Ed.: Kurt J.
Isselbacher, M.D.
et al., Editors; McGraw-Hill, Inc., 1998. Pp. 1405-06.
THE MERCK MANUAL, 17th Ed.: Robert Berkow and Mark Beers, Editors;
Merck
Research Laboratories; 1999. P. 1798.
TEXTBOOK OF DERMATOLOGY, 5th Ed.: R.H. Champion et al., Editors;
Blackwell
Scientific Publications, 1992. Pp. 2018-23.
BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, Editor-In-Chief;
Blackwell
Scientific Publications, 1990. Pp. 1087-89.
NELSON TEXTBOOK OF PEDIATRICS, 15th Ed.: Richard E. Behrman, Editor;
W.B.
Saunders Company, 1996. Pp. 1440-41.
DICTIONARY OF MEDICAL SYNDROMES, 3rd Ed.: Sergio I. Magalini, Sabina C.
Magalini,
and Giovanni de Francisci, Editors; J.B. Lippincott Company, 1990. Pp.
637-38.
18 STEPS TO PREVENTION FOR LOWER EXTREMITIES. S. Thiadens, R.N.;
National
Lymphadema Network Special Circular (1998).
CDP TREATMENT OF SMALL CHILDREN AND INFANTS WITH PRIMARY (CONGENITAL)
LYMPHEDEMA.
G. Klose; National Lymphedema Network Newsletter (Jan-Mar 1998; 10(1)).
Pp. 1-5.
TREATMENT OF LYMPHEDEMA WITH COMPLETE DECONGESTIVE PHYSIOTHERAPY. J.E.
Zuther;
National Lymphedema Network Newsletter (Apr-Jun 1999; 11(2)). Pp. 3-8.
PRIMARY LYMPHEDEMA. S.G. Rockson, Author; In: Currenty Therapy in
Vascular
Surgery, 4th Ed.: C. B. Ernst et al., Editors; Mosby.
LYMPHEDEMA: A REVIEW OF THE RELEVANT ANATOMY AND PHYSIOLOGY OF THE
LYMPHATICS.
A. Szuba et al.; Vascular Medicine (1997; 2). Pp. 321-26.
LYMPHEDEMA: A REVIEW OF DIAGNOSTIC TECHNIQUES AND THERAPEUTIC OPTIONS.
A. Szuba
et al.; Vascular Medicine (1998; 3). Pp. 145-56.
HEREDITARY LATE-ONSET LYMPHEDEMA WITH PLEURAL EFFUSION AND LARYNGEAL
EDEMA. F.A.
Herbert et al.; Arch Intern Med (May 1983; 143(5)). Pp. 913-15.
HEREDITARY LYMPHEDEMA AND DISTICHIASIS. T. Kolin et al.; Arch
Ophthalmol (Jul
1991; 109(7)). Pp. 980-81.
LYMPHANGIOSARCOMA IN CHRONIC HEREDITARY OEDEMA (MILROY'S DISEASE). L.A.
Brostrom
et al.; Ann Chir Gynaecol (1989; 78(4)). Pp. 320-23.
CONGENITAL HEREDITARY LYMPHEDEMA (NONNE/MILROY). D.D. Farhud et al.;
Padiatrpa
Padol (1989; 24(4)). Pp. 305-07.
.........................................................................................
THE LYMPH SYSTEM
The diagram to the below shows the lymphatic system and related organs. (Cancer Research UK) 
===========================================================
HERE
IS AN EXCELLANT ARTICLE FROM THE NATIONAL CANCER INSTITUTE INFORMATION
FROM
PDQCancerMail from the National Cancer Institute Information from PDQ
for
Patients
Lymphedema
** INTRODUCTION ** This patient summary is adapted from the summary on
lymphedema written by cancer experts for health professionals. This and
other
credible information about cancer treatment, screening, prevention,
supportive
care, and ongoing trials, is available from the National Cancer
Institute.
Lymphedema is the buildup of lymph (a fluid that helps fight infection
and
disease) in the fatty tissues just under the skin. The buildup of lymph
causes
swelling in specific areas of the body, usually an arm or leg, with an
abnormally high amount of tissue proteins, chronic inflammation, and
thickening
and scarring of tissue under the skin. Lymphedema is a common
complication of
cancer and cancer treatment and can result in long-term physical,
psychological,
and social issues for patients.
**OVERVIEW ** The lymphatic system consists of a network of specialized
lymphatic vessels and various tissues and organs throughout the body
that
contain lymphocytes (white blood cells) and other cells that help the
body fight
infection and disease. The lymphatic vessels are similar to veins but
have
thinner walls. Some of these vessels are very close to the skin surface
and can
be found near veins; others are just under the skin and in the deeper
fatty
tissues near the muscles and can be found near arteries. Muscles and
valves
within the walls of the lymphatic vessels near the skin surface help
pick up
fluid and proteins from tissues throughout the body and move the lymph
in one
direction, toward the heart. Lymph is slowly moved through larger and
larger
lymphatic vessels and passes through small bean-shaped structures
called lymph
nodes. Lymph nodes filter substances that can be harmful to the body
and contain
lymphocytes and other cells that activate the immune system to fight
disease.
Eventually, lymph flows into one of two large ducts in the neck region.
The
right lymphatic duct collects lymph from the right arm and the right
side of the
head and chest and empties into the large vein under the right collar
bone. The
left lymphatic duct or thoracic duct collects lymph from both legs, the
left arm
and the left side of the head and chest and empties into the large vein
under
the left collar bone. The lymphatic system collects excess fluid and
proteins
from the body tissues and carries them back to the bloodstream.
Proteins and
substances too big to move through the walls of veins can be picked up
by the
lymphatic vessels because they have thinner walls. Edema may occur when
there is
an increase in the amount of fluid, proteins, and other substances in
the body
tissues because of problems in the blood capillaries and veins or a
blockage in
the lymphatic system.
Lymphedema may be either primary or secondary
Primary lymphedema is a rare inherited condition in which lymph nodes
and lymph
vessels are absent or abnormal. Secondary lymphedema can be caused by a
blockage
or cut in the lymphatic system, usually the lymph nodes in the groin
area and
the arm pit. Blockages may be caused by infection, cancer, or scar
tissue from
radiation therapy or surgical removal of lymph nodes. This summary
discusses
secondary lymphedema.
Acute versus gradual-onset lymphedema
There are four types of acute lymphedema. The first type of acute
lymphedema is
mild and lasts only a short time, occurring within a few days after
surgery to
remove the lymph nodes or injury to the lymphatic vessels or veins just
under
the collar bone. The affected limb may be warm and slightly red, but is
usually
not painful and gets better within a week after keeping the affected
arm or leg
supported in a raised position and by contracting the muscles in the
affected
limb (for example, making a fist and releasing it). The second type of
acute
lymphedema occurs 6 to 8 weeks after surgery or during a course of
radiation
therapy. This type may be caused by inflammation of either lymphatic
vessels or
veins. The affected limb is tender, warm or hot, and red and is treated
by
keeping the limb supported in a raised position and taking
anti-inflammatory
drugs. The third type of acute lymphedema occurs after an insect bite,
minor
injury, or burn that causes an infection of the skin and the lymphatic
vessels
near the skin surface. It may occur on an arm or leg that is
chronically
swollen. The affected area is red, very tender, and hot and is treated
by
supporting the affected arm or leg in a raised position and taking
antibiotics.
Use of a compression pump or wrapping the affected area with elastic
bandages
should not be done during the early stages of infection. Mild redness
may
continue after the infection. The fourth and most common type of acute
lymphedema develops very slowly and may become noticeable 18 to 24
months after
surgery or not until many years after cancer treatment. The patient may
experience discomfort of the skin or aching in the neck and shoulders
or spine
and hips caused by stretching of the soft tissues, overuse of muscles,
or
posture changes caused by increased weight of the arm or leg.
Temporary versus chronic lymphedema
Temporary lymphedema is a condition that lasts less than 6 months. The
skin
indents when pressed and stays indented, but there is no hardening of
the skin.
A patient may be more likely to develop lymphedema if he or she has: -
surgical
drains that leak protein into the surgical site - inflammation - an
inability to
move the limb(s) - temporary loss of lymphatic function - blockage of a
vein by
a blood clot or inflammation of a vein.
Chronic (long-term) lymphedema
is the most difficult of all types of edema to treat. the damaged
lymphatic
system of the affected area is not able to keep up with the increased
need for
fluid drainage from the body tissues. This may happen: - after a tumor
recurs or
spreads to the lymph nodes - after an infection and/or injury of the
lymphatic
vessels - after periods of not being able to move the limbs - after
radiation
therapy or surgery - when early signs of lymphedema have not been able
to be
controlled - when a vein is blocked by a blood clot. A patient who is
in the
early stages of developing lymphedema will have swelling that indents
with
pressure and stays indented but remains soft. The swelling may easily
improve by
supporting the arm or leg in a raised position, gently exercising, and
wearing
elastic support garments. Continued problems with the lymphatic system
cause the
lymphatic vessels to expand and lymph flows back into the body tissues,
making
the condition worse. This causes pain, heat, redness, and swelling as
the body
tries to get rid of the extra fluid. The skin becomes hard and stiff
and no
longer improves with raised support of the arm or leg, gentle exercise,
or
elastic support garments. Patients with chronic lymphedema are at
increased risk
of infection. No effective treatment is yet available for patients who
have
advanced chronic lymphedema. Once the body tissues have been repeatedly
stretched, lymphedema may recur more easily.
Risk factors
Factors that can lead to the development of lymphedema include
radiation therapy
to an area where the lymph nodes were surgically removed, problems
after surgery
that cause inflammation of the arm or leg, the number of lymph nodes
removed in
surgery, and being elderly.
Patients who are at risk for lymphedema are those with: - Breast cancer
if they
have received radiation therapy or had lymph nodes removed. Radiation
therapy to
the underarm area after surgical removal of the lymph nodes and the
number of
lymph nodes removed increases the risk of lymphedema. - Surgical
removal of
lymph nodes in the underarm, groin, or pelvic regions. - Radiation
therapy to
the underarm, groin, pelvic, or neck regions. - Scar tissue in the
lymphatic
ducts or veins, under the collar bones, caused by surgery or radiation
therapy.
- Cancer that has spread to the lymph nodes in the neck, chest,
underarm,
pelvis, or abdomen. - Tumors growing in the pelvis or abdomen that
involve or
put pressure on the lymphatic vessels and/or the large lymphatic duct
in the
chest and block lymph drainage. - An inadequate diet or those who are
overweight. These conditions may delay recovery and increase the risk
for
lymphedema.
Diagnosis
Specific criteria for diagnosing lymphedema do not yet exist. About
half of
patients with mild edema describe their affected arm or leg as feeling
heavier
or fuller than usual. To evaluate a patient for lymphedema, a medical
history
and physical examination of the patient should be completed. The
medical history
should include any past surgeries, problems after surgery, and the time
between
surgery and the onset of symptoms of edema. Any changes in the edema
should be
determined as well as any history of injury or infection. Knowing the
medications a patient is taking is also important for diagnosis.
Prevention
Patients at risk for lymphedema should be identified early, monitored,
and
taught self-care. A patient may be more likely to develop lymphedema if
he or
she eats an inadequate diet, is overweight, is inactive, or has other
medical
problems. To detect the condition early, the following should be
examined: -
comparison of actual weight to ideal weight - measurements of the arms
and legs
- protein levels in the blood - ability to perform activities of daily
living -
history of edema, previous radiation therapy, or surgery - other
medical
illnesses, such as diabetes, high blood pressure, kidney disease, heart
disease,
or phlebitis (inflammation of the veins). It is important that the
patient know
about his or her disease and the risk of developing lymphedema. Poor
drainage of
the lymphatic system due to surgery to remove the lymph nodes or
radiation
therapy may make the affected arm or leg more susceptible to serious
infection.
Even a small infection may lead to serious lymphedema. Patients should
be taught
about arm, leg, and skin care after surgery and/or radiation (see Table
1
below). It is important that patients take precautions to prevent
injury and
infection in the affected arm or leg, since lymphedema can occur 30 or
more
years after surgery. Breast cancer patients who follow instructions
about skin
care and proper exercise after mastectomy are less likely to experience
lymphedema. Lymphatic drainage is improved during exercise, therefore
exercise
is important in preventing lymphedema. Breast cancer patients should do
hand and
arm exercises as instructed after mastectomy. Patients who have surgery
that
affects pelvic lymph node drainage should do leg and foot exercises as
instructed. The doctor decides how soon patients should start
exercising after
surgery. Physiatrists (doctors who specialize in physical medicine and
rehabilitation) or physical therapists should develop an individualized
exercise
program for the patient.
------------------------------------------------------------------------
| LYMPHEDEMA, HEREDITARY, I |
Alternative titles; symbols
NONNE-MILROY LYMPHEDEMAA number sign (#) is used with this entry because hereditary lymphedema type I is caused by mutation in the FLT4 gene (136352), which encodes the vascular endothelial growth factor receptor-3.
See hereditary lymphedema type II, also known as Meige lymphedema (153200), and the lymphedema-distichiasis syndrome (153400) for disorders with related phenotypes.
Milroy
(1928), a physician in Omaha, Nebraska, described the
disorder in a family
in which many of the affected persons were prominent in public and
professional
life. Rosen et
al. (1962) observed congenital chylous ascites in an affected
infant whose
father had recurrent swelling of the scrotum beginning at the age of 20
years.
Marked loss of albumin into the intestinal tract with consequent
hypoproteinemia
was demonstrated. In 2 patients, Hurwitz
and Pinals (1964) observed persistent bilateral pleural
effusion in which
the protein content of the pleural fluid was high. Esterly
(1965) described a family with 15 affected members of 3
generations. One
child had striking congenital edema of the hands as a main feature and
a second
had similar swelling of the hands, as well as bilateral involvement of
the legs
and feet. A sib of the proposita had no apparent lymphedema, although 2
of his 4
children had bilateral swelling of the legs and feet. He was regarded
at first
as a 'skipped' generation similar to those noted in previous pedigrees
of Milroy
disease. Closer examination, however, demonstrated a definite 3 x 5 cm
area of
slight edema on the medial aspect of the left lower leg. This area was
warm to
the touch and could be pitted against the underlying tibia. High blood
flow in
the leg affected by congenital lymphedema has been thought to be due to
accumulation of vasodilatory metabolites. Lymphedematous legs generally
feel
warm and the patients have warm feet. The proposita in the family
reported by Esterly
(1965) could recover the newspaper from her front walk in her
bare feet in
winter without discomfort. Esterly
(1965) reviewed 22 previously documented pedigrees which,
with his own
family, gave a total of 152 affected persons. 
Ferrell
et al. (1998) studied 13 lymphedema families from the U.S.
and Canada. All
members of these families were of western European ancestry. In the 13
families,
105 individuals were classified as affected, with a male:female ratio
of 1:2.3.
The age of onset of lymphedema ranged from prenatal (diagnosed by
ultrasound) to
age 55 years. When affected x normal matings were analyzed, 76 of 191
children
were affected, yielding a penetrance of 80%.
Holberg
et al. (2001) performed a complex segregation analysis and a
genomewide
search for linkage in 6 previously described families with Milroy
congenital
lymphedema. Results confirmed that Milroy lymphedema is generally
inherited as a
dominant condition, but this mode of inheritance did not account for
all
observed familial correlations. The authors suggested that shared
environmental
or additional genetic factors may also be important in explaining the
observed
familial aggregation.
In
linkage studies of 3 multigeneration families
demonstrating hereditary lymphedema segregating as an autosomal
dominant with
incomplete penetrance, Ferrell
et al. (1998) demonstrated a 2-point lod score of 6.1 at
theta = 0.0 for
marker D5S1354 and a maximum multipoint lod score of 8.8 at marker
D5S1354
located at 5q34-q35. Linkage analysis in 2 additional families using
markers
from the linked region showed 1 family consistent with linkage to
distal
chromosome 5; in the second family, linkage to 5q was excluded for all
markers
in the region.
Evans
et al. (1999) carried out a genomewide search in a
4-generation North
American family with what they termed 'dominantly inherited primary
congenital
lymphedema.' They established linkage to markers from the 5q35.3 region
in this
family and in 4 additional British families. The locus appeared to be
situated
in the most telomeric region of 5q35.3. No recombination was observed
with
D5S408 (lod = 10.03) and D5S2006 (lod = 8.46), with a combined
multipoint score
of 16.55. Four unaffected subjects were identified as gene carriers and
provided
an estimated penetrance ratio of 0.84 for this disorder.
In a family with hereditary lymphedema, Ferrell et al. (1998) identified a mutation in the FLT4 gene (136352.0001). In several families with autosomal dominant hereditary lymphedema, Karkkainen et al. (2000) identified different mutations in the FLT4 gene (see, e.g., 136352.0002).
Congenital lymphedema is autosomal dominant in the pig (9,10:Van der Putte, 1978, 1978).
Cassandra
L. Kniffin - reorganized : 11/19/2003
Sonja A. Rasmussen - updated : 3/12/2001
Victor A. McKusick - updated : 2/10/1999
Victor A. McKusick - updated : 1/6/1999
*Link no longer available*
------------------------------------
EXTERNAL LINKS:
---------------------------------------
Hereditary lymphedema I
Raul Martinez, MD
Unidad Regiomontana de Diagn?stico, Monterrey, N.L. Address correspondence to Raul Martinez (rmtzsal@intercable.net), Unidad Regiomontana de Diagnostico, 5 de Mayo # 403 Pte., Monterrey, N.L., México. CP. 64000.
Synonyms:
Nonne-Milroy
lymphedema1,2.
Lymphedema, early-onset. Primary congenital lymphedema.
Definition:
Lymphedema is
a chronic tissue swelling
that is most commonly manifested in
a limb. This
condition results from impaired lymph drainage
in the
presence of normal capillary filtration. It may
be either
primary in type, which implies an intrinsic
abnormality of
the lymph-conducting pathways or, secondary
in type, which
implies that external factors such as
radiotherapy, severe
infection, or surgical excision have
damaged lymph
drainage routes. Most forms of primary
lymphedema are thought
to be caused by a congenital abnormality
of the lymphatic
system.
True
congenital lymphedema, or hereditary lymphedema
type I (OMIM
153100),
usually presents either at, or soon
after, birth and
may be associated with other congenital
malformations3,4,5,6.
Onset of clinical symptoms in hereditary lymphedema type II (OMIM 153200) usually occurs during or near either puberty or the menopause. In 1962 was reported a congenital chylous ascites in an affected infant, whose father had recurrent swelling of the scrotum beginning at the age of 20 years7. In 1964 pleural effusion was observed8. In 1965, Esterly described one child with congenital edema of the hands, as well as bilateral involvement of the legs and feet9
History:
Although
postnatal clinical diagnosis of this condition is relatively easy,
there is only
one prenatally diagnosed case described in the literature10.
Prevalence:
Nonne-Milroy
lymphedema or hereditary lymphedema I is a
relatively rare condition,
whose occurrence is estimated to be around 1-2:10,000
Etiology:
The
defect shows an autosomal dominant pattern of inheritance with reduced
penetrance (80-84%), variable expressivity and variable age of onset
from
prenatal to 55 years. The
disease has been mapped to the telomeric part of chromosome 5q, in the
region
5q34-q35.
Pathogenesis:
It
has recently been demonstrated that this region (5q34-q35)
contains
the FLT4 locus encoding the vascular endothelial growth factor
receptor-3
(VEGFR-3), whose mutations interfere with normal vascular lymphatic
function11,12.
Sonographic
findings: The
disease has variable expressivity and must be suspected in those
fetuses with
distal subcutaneous edema of the extremities, most frequently of the
lower
limbs, but the hands can also be involved. Findings can be present in
one
extremity or in all of them, and there is no concordance in the time of
appearance and degree of involvement of each extremity. Occasionally,
persistent
or transient pleural effusion and ascites can be found.
The rest of the examination is normal.
Differential
diagnosis: The
following dysmorphic syndromes must be considered: Turner, Noonan,
microcephaly-lymphedema, and hydrops.
Associated
anomalies:
There are reports of associations with distichiasis4,
hydroceles, atrial septal defect, and characteristic facial changes6
Prognosis:
Edema, particularly severe below the waist, sometimes
complicated with
papillomatosis and nail changes.
Management:
Several
individuals ware compression stockings, which
are
effective in containing the edema, whereas those
who are
more severely affected attend hospital for
compression
pumping to reduce limb size prior to
being fitting for
compression hosiery.
http://www.thefetus.net/page.php?id=358
------------------------------------------------------------------------
| LYMPHEDEMA, HEREDITARY, II |
Alternative titles; symbols
MEIGE LYMPHEDEMAA number sign (#) is used with
this entry because of evidence that hereditary
lymphedema type II is caused by mutation in the forkhead family
transcription
factor gene MFH1 (FOXC2; 602402).
Allelic disorders with overlapping features include the
lymphedema-distichiasis
syndrome (153400),
lymphedema and ptosis (153000),
and lymphedema and yellow nail syndrome (153300).
Also see hereditary lymphedema type I, or Milroy disease (153100).
Edema, particularly severe
below the waist, develops about the time of
puberty. Meige
(1898) described 8 cases in 4 generations without
male-to-male transmission.
Goodman (1962)
reported the condition in 2 sisters and a brother with presumed normal
parents
who were not known to be related. Herbert
and Bowen (1983) described a kindred with many cases of
lymphedema of
postpubertal onset. Involvement of the upper limbs (as well as the
lower limbs),
face, and larynx and, in one, a persistent pleural effusion were
notable
features. Scintilymphangiography indicated paucity or absence of lymph
nodes in
the axillae and above the inguinal ligaments. Chronic facial swelling
resulted
in a characteristic appearance of affected members including puffiness,
shiny
skin, deep creases, and, in some, excessive wrinkling. Emerson
(1966) noted similar facial features and remarked on the
possible erroneous
diagnosis of myxedema.
Herbert
and
Bowen (1983) noted the difficulties of nosology. For example,
because
lymphedema and yellow nail syndrome has yellow or dystrophic nails as a
variable
feature, this could be the same disorder. They pointed also to the
association
of late-onset lymphedema with deafness (Emberger
et al., 1979) and with primary pulmonary hypertension and
cerebrovascular
malformations (152900;
Avasthey and
Roy, 1968).
Figueroa
et
al. (1983) reported the association of cleft palate. In their
family, the
mother, with only lymphedema praecox of the legs, gave birth to 5 sons,
3 of
whom had both lymphedema of the legs and cleft palate. A mild form of
lymphedema
affecting mainly the medial aspect of both ankles in a 21-year-old son
was
pictured.
Andersson
et
al. (1995) described a family in which 3 individuals, a
grandmother, her son
and her grandson, had onset of lymphedema in their mid-20s or 30s. The
grandson
was 23 years old when he had his first episode of lymphedema, which was
thought
to be due to thrombophlebitis. During the ensuing decade, he had
episodic waxing
and waning of lymphedema of both lower limbs and was treated with
anticoagulant
therapy. At the age of 35, he developed lymphangiosarcoma on the inner
right
thigh and died of metastases some months later. Lymphangiosarcoma,
usually
associated with postmastectomy lymphedema, had not been described
previously in
late-onset hereditary lymphedema. Andersson
et al. (1995) raised the question of whether a genetic
predisposition to
malignancy combined with the lymphedema was etiologically significant.
There
seemed to be an unusually high frequency of cancer (uterine, colon,
lung,
prostate, breast, and bone) in the proband's family.
Finegold et al. (2001) found a mutation in the FOXC2 gene (602402.0007) in a family with Meige lymphedema and also in a family with yellow nail syndrome.
Finegold et al. (2001) noted that the phenotypic classification of dominantly inherited lymphedema includes Milroy disease (hereditary lymphedema I), Meige lymphedema (hereditary lymphedema II), lymphedema-distichiasis syndrome, lymphedema and ptosis, and yellow nail syndrome. The phenotypes reported in their 11 families overlapped the findings reported in Meige lymphedema, lymphedema-distichiasis syndrome, lymphedema and ptosis, and yellow nail syndrome, but not in Milroy disease. Milroy disease is associated with mutation in the FLT4 gene (136352), whereas mutations in the FOXC2 gene were observed in the 4 lymphedema syndromes that had phenotypic overlap.
Juchems (1963); Osterland (1961); Wheeler et al. (1981)
George E. Tiller - updated : 10/22/2001
Victor A. McKusick : 6/2/1986
carol : 11/19/2003
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=153200
=================
Join us as we work for lymphedema patients everywehere:
Advocates for Lymphedema
Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.
http://health.groups.yahoo.com/group/AdvocatesforLymphedema/
| Subscribe: | AdvocatesforLymphedema-subscribe@yahoogroups.com |
Pat O'Connor
Lymphedema People / Advocates for Lymphedema
=================
For information about Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema\
For Information about Lymphedema Complications
http://www.lymphedemapeople.com/wiki/doku.php?id=complications_of_lymphedema
For Lymphedema Personal Stories
http://www.lymphedemapeople.com/phpBB2/viewforum.php?f=3
For information about How to Treat a Lymphedema Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
For information about Lymphedema Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
For information about Exercises for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
For information on Infections Associated with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
For information on Lymphedema in Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphedema Glossary
http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing
=================
Lymphedema People - Support Groups
-----------------------------
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.
http://health.groups.yahoo.com/group/childrenwithlymphedema/
Subscribe: childrenwithlymphedema-subscribe@yahoogroups.com
......................
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.
Come join, be a part of the family!
http://health.groups.yahoo.com/group/lipedema_lipodema_lipoedema/?yguid=209645515
Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com
......................
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.
http://health.groups.yahoo.com/group/menwithlymphedema/
Subscribe: menwithlymphedema-subscribe@yahoogroups.com
......................
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/
Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com
......................
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/
Subscribe: lymphaticdisorders-subscribe@yahoogroups.com
=================
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
Exercises
for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
Diuretics
are not for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema
Lymphedema
People Online Support
Groups
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_people_online_support_groups
Lipedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lipedema
Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
Lymphedema
and Pain Management
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pain_management
Manual
Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)
Infections
Associated with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
How
to Treat a Lymphedema Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
Fungal
Infections Associated with
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema
Lymphedema
in Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphoscintigraphy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphoscintigraphy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Extraperitoneal
para-aortic lymph node dissection (EPLND)
Axillary
node biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=axillary_node_biopsy
Sentinel
Node Biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy
Small
Needle Biopsy - Fine Needle Aspiration
http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Lymphedema
Gene FOXC2
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2
Lymphedema Gene VEGFC
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc
Lymphedema Gene SOX18
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18
Lymphedema
and Pregnancy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy
Home page: Lymphedema People
http://www.lymphedemapeople.com
Page Updated: Dec. 3, 2011