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?

What is Marfan syndrome?

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.

What causes Marfan syndrome?

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.

Is Marfan syndrome inherited?

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.

Is there a cure for Marfan syndrome?

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.

What do you do to accomplish this goal?

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.

How do you diagnose Marfan syndrome?

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.

Why can't I just get a genetic test to diagnose Marfan syndrome if it is a genetic condition?

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.

When and why should genetic testing be done?

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.

Does your Center see other patients, besides those with Marfan syndrome?

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.

What are the related 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.

What is Loeys-Dietz syndrome?

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.

Why is there an emphasis on vascular EDS in the program?

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.

Who can be seen through the program?

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.

Where is the Marfan syndrome 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.

What can I do to prepare for my appointment?

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.

Do you accept self-referrals?

Yes, we accept both physician and self-referrals.

Are you able to determine over the phone as to whether I should be seen?

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.

How can appointments through the Marfan Syndrome and Related Conditions Program be scheduled?

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.

Will my insurance cover appointments through the Center for Marfan Syndrome?

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.

What if my physician refuses to refer me or my insurance refuses to pay for a visit?

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.

Is there research going on at Hoag?

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.