Marfan syndrome is an inherited disorder of the connective tissue that
causes abnormalities of a child's eyes, cardiovascular system, and
musculoskeletal system. It is named for the French pediatrician, Antoine
Marfan (1858-1942), who first described it in 1896.
Marfan syndrome affects three major organ systems of the body: the heart
and circulatory system, the bones and muscles, and the eyes. The genetic
mutation responsible for Marfan was discovered in 1991. It affects the
body's production of fibrillin, which is a protein that is an
important part of connective tissue. Fibrillin is the primary component of
the microfibrils that allow tissues to stretch repeatedly without
weakening. Because the child's fibrillin is abnormal, his or her
connective tissues are looser than usual, which weakens or damages the
support structures of the entire body.
The most common external signs associated with Marfan syndrome include
excessively long arms and legs, with the child's arm span being
greater than his or her height. The fingers and toes may be long and
slender, with loose joints that can be bent beyond their normal
limits. This unusual flexibility is called hypermobility. The
child's face may also be long and narrow, and he or she may have a
noticeable curvature of the spine. It is important to note, however, that
children with Marfan vary widely in the external signs of their disorder
and in their severity; even two children from the same
may look quite different. Most of the external features of Marfan
syndrome become more pronounced as the child gets older, so that diagnosis
of the disorder is often easier in adults than in children. In many cases,
the child may have few or very minor outward signs of the disorder, and
the diagnosis may be missed until the child develops vision problems or
Marfan syndrome by itself does not affect a child's
or ability to learn. There is, however, some clinical evidence that
children with Marfan have a slightly higher rate of hyperactivity and
attention-deficit disorder (ADD) than the general population. In addition,
a child with undiagnosed nearsightedness related to Marfan may have
difficulty seeing the blackboard or reading printed materials, and thus do
poorly in school.
Marfan syndrome affects males and females equally, and appears to be
distributed equally among all races and ethnic groups. The rate of
mutation of the fibrillin gene, however, appears to be related to the age
of the child's father; older fathers are more likely to have new
mutations appear in chromosome 15.
Marfan syndrome is sometimes called arachnodactyly, which means
"spider-like fingers" in Greek, since one of the
characteristic signs of the disease is disproportionately long fingers and
It is estimated that one person in every 3000-5000 has Marfan syndrome, or
about 50,000 people in the United States. Marfan syndrome is one of the
more common inheritable disorders.
Causes and symptoms
Marfan syndrome is caused by a single gene for fibrillin on chromosome 15,
which is inherited in most cases from an affected parent. Between 15 and
25 percent of cases result from spontaneous mutations. Mutations of the
fibrillin gene (FBNI) are unique to each family affected by Marfan, which
makes rapid genetic diagnosis impossible, given present technology. The
syndrome is an autosomal dominant disorder, which means that someone who
has it has a 50 percent chance of passing it on to any offspring.
Another important genetic characteristic of Marfan syndrome is variable
expression. This term means that the mutated fibrillin gene can produce a
variety of symptoms of very different degrees of severity, even in members
of the same family.
The most important complications of Marfan are those affecting the heart
and major blood vessels; some are potentially life-threatening. About 90
percent of children with Marfan will develop cardiac complications,
Marfan syndrome causes an increase in the length of the child's
bones, with decreased support from the ligaments that hold the bones
together. As a result, the child
may develop various deformities of the skeleton or disorders related to
the relative looseness of the ligaments.
Children with Marfan syndrome also can experience spinal disorders,
Disorders of the chest and lower body of children with Marfan include:
Although the visual problems that are related to Marfan syndrome are
rarely life-threatening, they are important in that they may be the
child's first indication of the disorder. Eye disorders related to
the syndrome include the following:
Other disorders associated with Marfan syndrome include:
Prospective parents with a family history of Marfan syndrome should check
with their doctor concerning genetic counseling. Also a doctor should be
called if a child has symptoms suggestive of Marfan syndrome.
Presently, there is no objective diagnostic test for Marfan syndrome, in
part because the disorder does not produce any measurable biochemical
changes in the child's blood or body fluids, or cellular changes
that can be detected from a tissue sample. Although researchers in
molecular biology are currently investigating the FBNI gene through a
process called mutational analysis, it is presently not useful as a
diagnostic test because there is evidence that there can be mutations in
the fibrillin gene that do not produce Marfan. Similarly, there is no
reliable prenatal test, although some physicians have used ultrasound to
try to determine the length of fetal limbs in at-risk pregnancies.
The diagnosis is made by taking a family history and a thorough
examination of the child's eyes, heart, and bone structure. The
examination should include an echocardiogram taken by a cardiologist, a
slit-lamp eye examination by an ophthalmologist, and a work-up of the
child's spinal column by an orthopedic specialist. In terms of the
cardiac examination, a standard electrocardiogram (EKG) is not sufficient
for diagnosis; only the echocardiogram can detect possible enlargement of
the aorta. The importance of the slit-lamp examination is that it allows
the doctor to detect a dislocated lens, which is a significant indication
of the syndrome.
The symptoms of Marfan syndrome in some children resemble the symptoms of
homocystinuria, which is an inherited disorder marked by extremely high
levels of homocystine in the child's blood and urine. This
possibility can be excluded by a urine test.
In other cases, the diagnosis remains uncertain because of the mildness of
the child's symptoms, the absence of a family history of the
syndrome, and other variables. These borderline conditions are sometimes
referred to as marfanoid syndromes.
The treatment and management of Marfan is tailored to the specific
symptoms of each child. Some children find that the syndrome has little
impact on their overall lifestyle; others have found their lives centered
on the disorder.
After a child has been diagnosed with Marfan, he or she should be
monitored with an echocardiogram every six months until it is clear that
the aorta is not growing larger. After that, he or she should have an
echocardiogram once a year. If the echocardiogram does not allow the
physician to visualize all portions of the aorta, CT (
) or MRI (
magnetic resonance imaging
) may be used. In cases involving a possible aortic dissection, the child
may be given a TEE (transesophageal echocardiogram).
Medications. A child with Marfan may be given drugs called beta-blockers
to slow down the rate of aortic enlargement and decrease the risk of
dissection by lowering the blood pressure and decreasing the forcefulness
of the heartbeat. The most commonly used beta-blockers in chidren with
Marfan are propranolol (Inderal) and atenolol (Tenormin). Children who are
allergic to beta-blockers may be given a calcium blocker such as
Because children with Marfan are at increased risk for infective
endocarditis, they must take a prophylactic dose of an antibiotic before
having dental work or minor surgery, as these procedures may allow
bacteria to enter the bloodstream. Penicillin and amoxicillin are the
most often used.
Surgical treatment. Surgery may be necessary if the width of the
child's aorta increases rapidly or reaches a critical size (about 2
inches [5 cm]). The most common surgical treatment involves replacing the
child's aortic valve and several inches of the aorta itself with a
composite graft, which is a prosthetic heart valve sewn into one end of a
Dacron tube. This surgery has been performed widely since about 1985; most
children who have had a composite graft have not needed additional
surgery. Children who have had a valve replaced must take an anticoagulant
medication, usually warfarin (Coumadin), in order to minimize the
possibility of a clot forming on the prosthetic valve.
Children diagnosed with Marfan should be checked for scoliosis by their
pediatricians at each annual physical examination. The doctor simply asks
the child to bend forward while the back is examined for changes in the
curvature. In addition, the child's spine should be x rayed in
order to measure the extent of scoliosis or kyphosis. The curve is
measured in degrees by the angle between the vertebrae as seen on the x
ray. Curves of 20 degrees or less are not likely to become worse. Curves
between 20 and 40
Five clinical signs of Marfan syndrome: (left to right) pectus
excavatum, positive thumb sign, positive elbow sign, normal spine
compared with scoliosis, normal anatomy compared with kyphosis.
(Illustration by Argosy, Inc.)
degrees are likely to increase in children or adolescents. Curves of 40
degrees or more are highly likely to worsen, even in an adult, because the
spine is so badly imbalanced that the force of gravity will increase the
Scoliosis between 20 and 40 degrees in children is usually treated with a
back brace. The child must wear this appliance about 23 hours a day until
growth is complete. If the spinal curvature increases to 40 or 50 degrees,
the child may require surgery in order to prevent lung problems, back
pain, and further deformity. Surgical treatment of scoliosis involves
straightening the spine with metal rods and fusing the vertebrae in the
Spondylolisthesis is treated with a brace in mild cases. If the slippage
is more than 30 degrees, the slipped vertebra may require surgical
Dural ectasia can be distinguished from other causes of back pain on an
MRI. Mild cases are usually not treated. Medication or spinal shunting to
remove some of the spinal fluid are used to treat severe cases.
Pectus excavatum and pectus carinatum can be treated by surgery. In pectus
excavatum, the deformed breastbone and ribs are raised and straightened by
a metal bar. After four to six months, the bar is removed in an outpatient
Protrusio acetabulae may require artificial hip joint surgery in adult
life, if the arthritic pains are severe.
Pain in the feet or limbs is usually treated with a mild analgesic such as
. Children with Marfan should consider wearing shoes with low heels,
special cushions, or orthotic inserts. Foot surgery is rarely necessary.
Children with Marfan should have a thorough eye examination, including a
slit-lamp examination, to test for dislocation of the lens as well as
nearsightedness. Dislocation can be treated by a combination of special
glasses and daily use of one percent atropine sulfate ophthalmic drops, or
Because children with Marfan are at increased risk of glaucoma, they
should have the fluid pressure inside the eye measured every year as part
of an eye examination. Glaucoma can be treated with medications or with
Cataracts are treated with increasing success by implant surgery. It is
important, however, to seek treatment at medical centers with eye surgeons
familiar with the possible complications of cataract surgery in children
with Marfan syndrome.
All children with Marfan should be taught to recognize the signs of
retinal detachment (sudden blurring of vision in one eye becoming
progressively worse without pain or redness) and ask their parents to seek
professional help immediately.
Children with Marfan should be evaluated by their dentist at each checkup
for crowding of the teeth and possible misalignment and referred to an
orthodontist if necessary.
—A condition characterized by abnormally long and slender fingers
—Dislocation of the lens of the eye. It is one of the most
important single indicators in diagnosing Marfan syndrome.
—A protein that is an important part of the structure of the
body's connective tissue. In Marfan's syndrome, the gene
responsible for fibrillin has mutated, causing the body to produce a
—Unusual flexibility of the joints, allowing them to be bent or
moved beyond their normal range of motion.
—An extreme, abnormal outward curvature of the spine, with a hump
at the upper back.
—An abnormality of the chest in which the sternum (breastbone) is
pushed outward. It is sometimes called "pigeon breast."
—An abnormality of the chest in which the sternum (breastbone)
sinks inward; sometimes called "funnel chest."
—An abnormal, side-to-side curvature of the spine.
is particularly harmful for children and adolescents with Marfan because
it increases their risk of emphysema.
Children and adolescents with Marfan may benefit from supportive
counseling regarding appearance, particularly if their symptoms are severe
enough to cause them to withdraw from social activities.
The prognosis for children with Marfan has improved markedly in recent
years. By 1995, the life expectancy of people with the syndrome increased
to 72 years, up from 48 years in 1972. This dramatic improvement is
attributed to new surgical techniques, improved diagnosis, and new
techniques of medical treatment.
The most important single factor in improving the child's prognosis
is early diagnosis. The earlier that a child can benefit from the new
techniques and lifestyle modifications, the more likely he or she is to
have a longer life expectancy.
Marfan syndrome that occurs because of spontaneous new mutations (15% to
25% of the cases) cannot be prevented. However, for prospective parents
with a family history of Marfan syndrome, genetic counseling is
recommended. Also, older fathers are more likely to have new mutations
appear in chromosome 15.
Families may wish to seek counseling regarding the effects of the syndrome
on relationships within the family. Many people respond with guilt,
, or blame when a genetic disorder is diagnosed in the family, or they may
overprotect the affected member. Support groups are often good sources of
information about Marfan; they can offer helpful suggestions about living
with it as well as emotional support.
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Annotated Research Guide to Internet References.
San Diego, CA: Icon Health Publications, 2004.
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San Diego, CA: Icon Health Publications, 2002.
PM Medical Health News.
21st Century Complete Medical
Guide to Marfan Syndrome: Authoritative Government Documents, Clinical
References, and Practical Information for Patients and Physicians.
Washington, DC: Progressive Management, 2004.
Pyeritz, Reed E., and Cheryll Gasner.
The Marfan Syndrome.
New York: National Marfan Syndrome, 1999.
New York: Kluwer Academic Publishers, 2004.
Alliance of Genetic Support Groups, 4301 Connecticut Avenue, Washington,
DC, 20008. (202) 652-5553. http://http:www.geneticalliance.org.
National Marfan Foundation, 22 Manhasset Avenue, Port Washington, NY,
11050-2023. (516) 883-8712, (800). 862-7326.
Marfan Syndrome, National Institutes of Health.