Frequently Asked Questions
What is Marfan syndrome?
What causes Marfan syndrome?
Is Marfan syndrome inherited?
Is there a cure for Marfan syndrome?
What do you do to accomplish this goal?
How do you diagnose Marfan syndrome?
Why can't I just get a genetic test to diagnose Marfan syndrome if
it is a genetic condition?
When and why should genetic testing be done?
Does your Center see other patients, besides those with Marfan syndrome?
What are the related conditions?
What is Loeys-Dietz syndrome?
What is Ehlers-Danlos syndrome?
Why is there an emphasis on vascular EDS in the program?
Who can be seen through the program?
Where is the Marfan syndrom program?
What can I do to prepare for my appointment?
Do you accept self-referrals?
Are you able to determine over the phone as to whether I should be seen?
How can appointments through the Marfan Syndrome and Related Conditions
Program be scheduled?
Will my insurance cover appointments through the Center for Marfan Syndrome?
What if my physician refuses to refer me or my insurance refuses to pay
for a visit?
Is there research going on at Hoag?
Marfan syndrome is disease caused by mutation in the FBN1 gene. FBN1 codes
for a protein called fibrillin-1 which is present throughout the body
which means that many parts of the body are affected. The most serious
of these effects is weakening of the aorta, the largest in the body, which
results in enlargement and tearing or rupture if not treated. The skeleton
is the most outwardly apparent effect as many of those affected will be
tall. Very flexible joints, curvature of the back, flat feet and deformities
of the chest wall are frequently seen. The eyes are often also involved
leading to lens dislocations, severe myopia and retinal detachments.
Marfan syndrome is due to a mutation in the FBN1 gene. Disease causing
mutations result in altered fibrillin-1 protein or a reduction in the
amount of normal fibrillin-1.
In most cases Marfan syndrome is inherited from one of the parents, however
in one-third to one-fourth of the cases, neither parent will have Marfan
syndrome. In these cases, the mutation in FBN1 is thought to be due to
an error when the DNA was copied in creating the egg or sperm. Marfan
syndrome is a dominantly inherited condition, meaning that only one of
the two copies of the FBN1 gene that each of us has needs to carry the
mutation to cause Marfan syndrome. This also means that there is a 50%
chance of passing on the mutated FBN1 gene when sperm and eggs are created.
Currently we cannot cure Marfan syndrome, however with proper care we believe
that life expectancy can be restored to near normal and quality of life
can be maintained. That is the goal of the Hoag Marfan program.
We work to arrive at the correct diagnosis. Once the diagnosis is made
we will work with you to live life in a way that will maximize its length
while also allowing you to live it to its fullest. We will provide surveillance
to help you choose the right time for prophylactic procedures. We will
also work with you to choose the appropriate type and medication that
will slow the growth of the aorta and we will guide you in finding the
right expert to treat you should problems arise.
Many of the features of Marfan syndrome occur in the general population,
so we look for a constellation of findings, particularly those which are
rare – enlargement of the aorta or dislocation of the lenses in
the eyes in reaching the diagnosis. Genetic testing and family history
are an important part of the diagnosis. Formal criteria called the modified
Ghent criteria have been developed (www.marfan.org/dx), however in some cases people with Marfan syndrome may not meet the criteria,
particularly children and teenagers.
Greater than 90% of patients with Marfan syndrome will have an identifiable
mutation in the FBN1 gene, however, in some cases we believe the mutation
may be in a region that is not sequenced with current techniques. Also,
certain types of mutations may not be apparent with current techniques.
On the other hand, there is variation in the FBN1 gene that does not result
in a harmful change in the fibrillin-1 protein or may result in a change
in the fibrillin-1 protein that causes a different set of symptoms. Although
many mutations and variations in the FBN1 gene have been cataloged, changes
the FBN1 gene cannot always be classified as disease causing without correlating
it with physical findings.
Genetic testing can be useful in discriminating between the conditions
if the physical characteristics are not clear. It can also be used in
cases where there remain questions about whether there is a genetic cause
after reviewing the physical findings. Even when the diagnosis is not
in doubt the results of genetic testing can be used for screening relatives
and for preimplantation diagnosis to reduce the risk of passing on the
disease to the next generation.
Yes, many conditions share features and concerns with Marfan syndrome and
the program has the expertise to care for those conditions and welcomes
patients with those conditions.
There are related conditions caused by mutations in other genes that result
features that are shared with Marfan syndrome. In particular these conditions
often also result in weakened blood vessels and aneurysm. Among these
conditions are Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome,
Shprintzen-Goldberg Syndrome, familial thoracic aortic aneurysm disorder
and bicuspid aortic valve disorder. In some cases, the conditions are
only known by the gene that is affected, ACTA2, MYH11, MYLK etc. In other
cases, the gene has not been identified yet, but the inherited nature
of the condition make us suspicious that there is a yet undiscovered causative gene.
These are a group of diseases of which its first two members were first
fully characterized by Bart Loeys and Hal Dietz. These were found to be
due to the receptors for the cell signaling protein TGF-beta. These genes
were TGFBR1 and TGFBR2. In contrast to Marfan syndrome the vasculature
can be more prone to tearing and the aneurysms are more widespread throughout
the body including blood vessels in the head and neck and branches in
the body smaller than the aorta. This necessitates broader surveillance.
Also, the weakness extends to the organs of the body including the uterus
and the intestine.
Subsequent to the initial description of Loeys-Dietz syndrome mutations
genes coding for protein in other places along the TGF-beta signaling
pathway have been found to cause aneurysms and have been grouped into
Loeys-Dietz syndrome. These include SMAD3, TGF-B2 and TGF-B3 and possibly
SMAD4. Although these conditions share many of the features first described
in Loeys-Dietz syndrome we are only just now working out what difference
may exist.
Ehlers-Danlos Syndrome (EDS) is a group of conditions that are best known
for flexibility of the joints. There are several variants which in many
cases are caused by different gene mutations. One of these is the vascular
type, which is sometimes referred to as EDS-IV or vEDS.
The common theme in the conditions treated by the program is the weakness
of the blood vessels. Among the types of Ehlers-Danlos Syndrome, the vascular
type is the only type with significant concerns about the blood vessels.
We strive to serve as a resource to address the needs of our patients,
so we do work closely with healthcare professionals with experience in
managing hypermobility and they may be resources for others with non-vascular
Ehlers-Danlos syndrome.
Patients with confirmed or suspected Marfan syndrome or a related condition.
If a diagnosis is already confirmed, the program offers monitoring and
supportive resources for patients and their families. Patients or physicians
suspecting a vascular related connective tissue disorder may request a
new patient consult through the program.
The Marfan Program operates and sees patients as part of the Jeffrey Carlton
Heart and Vascular Institute and the Matranga Aortic Center. Our offices
and clinics are located within the Heart and Vascular Institute. The various
specialist will have their offices within the Hoag Medical System.
For new and existing patients, it is critical to have copies of pertinent
medical records and all copies of previous cardiovascular imaging with
discs or CDs as well as the paper reports. Pertinent medical records include:
1. Completed New Patient Intake Forms including detailed family history
if available (link to downloadable forms) 2. Genetic testing results 3.
Echocardiogram (transthoracic and transesophageal) 4. CT Angiogram 5.
MR Angiogram 6. Operative Reports If any of these tests have been done
outside of Hoag please bring this to our attention when scheduling your
appointments so office staff may assist with gathering records.
Yes, we accept both physician and self-referrals.
Unfortunately, we are not able to diagnose anyone over the phone. If you
suspect that you have the Marfan syndrome related condition based on what
you have read or on the recommendation of your physician or other affected
family members, then it would be appropriate to be seen for an initial
evaluation. If you already carry a diagnosis of Marfan syndrome or another
connective tissue disorder and wish to be seen, this is certainly appropriate.
We are open to informational questions but understand that detailed medical
advice would only be appropriate after we have had a chance to meet you
and understand your medical condition in detail.
You may call the Hoag Marfan Syndrome and Related Conditions Program at
(949) 764-8468 Monday through Friday or simply email [email protected] for
additional information or to request an appointment.
There are so many different insurance companies and different policies
written by a company that if you have questions about your policy, we
ask that you call and speak with your insurance company directly. If you
belong to an HMO or other group health care plan that requires you to
get an authorization from your primary provider, please contact that individual.
Should your insurance company or primary care physician have questions
regarding your appointments, they may call us for information. Please
give them the (949) 764-8468 phone number. We will do what we can to assist
you in getting the evaluation you need.
We do not require a physician referral for you to be see at the Marfan
Program. However, with some insurances without a referral from your physician
and/or approval from the insurance company they will not cover the cost
of the visit. Under those circumstances we can work with you to try to
reduce the cost of the visit as much as possible by having as much of
the preliminary studies and evaluations done where your insurance will
provide coverage.
The Hoag Marfan and Related Conditions Program collaborates with the Marfan
Foundation (https://www.marfan.org/), as well as many of the leading researchers
around the world to help with the advancement of the understanding of
these conditions. We are members of the Montalcino Aortic Consortium https://www.montalcinoaorticconsortium.org/
and the International Bicuspid Aortic Valve Consortium. We encourage our
patients to add their information to the understanding of these diseases
but understand that there are some who are not comfortable sharing their
information.