International Federation Of Marfan Syndrome Organizations • December 2005 Volume 1 No. 1
This month MARFANWORLD E-NEWS focuses on: NORWAY
"In order to introduce a truly international form aspect on the IFMSO web site, each edition of the IFMSO Marfanworld e-newsletter will feature a different Marfan organization with text written the language of that country. The e-newsletter will focus on the different organizations in order to provide greater insight of the different groups' activities, and better communication between the world Marfan syndrome organizations. Some of the countries to be featured in upcoming newsletters will be South Africa, Australia, United States, and France."


The Norwegian
Marfan Organization


From left: Wenche Snekkevik, Elin Maria Askeland, Arild Jensen, Marianne Petersen, Ingrid H. Johansen, Atle Johannessen,
Tone Kvammen, Hilde Sande and Linn Hustad.

Den norske marfanforeningen har utviklet en reisebrosjyre, som nå skal distribueres ut til alle foreningene tilknyttet både EMSN og IFMSO. Dersom det er noen som ønsker den norske versjonene av brosjyren, ta kontakt med Marfanforeningen, c/o FFO, Postboks 4568, 0404 OSLO. E-post: info@marfan.no Ytterligere informasjon finner du på www.marfan.no


Foreningens formål

• Å være en landsomfattende forening for alle som er interessert i Marfan syndrom og andre marfanlignende tilstander.
• Å utøve en rådgivende, opplysende og hjelpende virksomhet til alle som er født med Marfan syndrom eller andre marfanlignende tilstander og deres familier.
• Å spre kunnskap om Marfan syndrom og andre marfanlignende tilstander til aktuelt fagpersonell.
• Å arbeide for at myndighetene skal få kjennskap til syndromets spesielle problemer.
• Å forbedre tilbudet til våre medlemmer i forhold til offentlige myndigheter.
• Å arbeide for å opprettholde et fagråd.
• Å utgi et medlemsblad.

The Norwegian Marfan Organization was founded in 1990, and today has 340 members. Norway is, together with Sweden, Denmark and Finland, a Scandinavian country. We have 4.5 million inhabitants.

The majority of our funding comes from the Norwegian government. We have a fund that provides support for members with needs for treatment related financial aid. We work to spread knowledge on the syndrome to members, health care providers, researchers and others with interests in Marfan syndrome. We arrange gatherings and workshops for our members. We also develop a magazine, which is circulated to members, hospitals and other health care providers. Representing our members in the dialog with the hospitals, government and other authorities, we try to improve the quality of life for people with Marfan syndrome. The Organizations board of directors consists of 9 members, and our medical advisory board consists of five specialists.

In 2002, we received a grant to revise our information folders. Shortly afterwards came the idea of also making an information brochure, to cover the needs for communicating basic emergency information when traveling. In collaboration with Gnist Design, The Norwegian Marfan Organization has developed a "Travelers Emergency Folder". It is designed to provide emergency information about Marfan syndrome in several different languages. Since it folds up like a small bus or train schedule, it is easy for people to carry it with them when traveling abroad. Despite its size however, it is written in 12 widely-spoken languages.

The EMSN was drawn into the development of the folder at an early stage, and our friends in Europe were involved in the process of how to best provide the information Therefore, it will be easy to comprehend on an international level among health providers.

We strongly believe in having an "international standard" for communicating basic information which can be easily recognized by health personnel world-wide in times of emergency. To achieve this goal, it is a big step in the right direction that IFMSO has approved of this work, and wants to see it developed even further. We hope all of you can make use of our folder, and maybe also help us in translating the words into other languages that are needed for covering traveling patterns around the world. Maybe a future plan can be for the IFMSO countries to have a standard "Travelers Emergency Information folder" for traveling based on the continent one might wish to visit. Please let us hear from you in this matter!

We feel honored to have both EMSN and IFMSO on our team. Thank you! If you want to know more about us, visit www.marfan.no

Best wishes for the holiday!

Wenche Snekkevik, Chair


Summary Report of the 7th International Marfan symposium

September marked the 7th International Marfan symposium held in Ghent, Belgium. Thanks to Bart Loeys, Josephine Grima, Julie De Backer and Anne De Paepe, we have the following summary of the meeting presentations:
The historical and picturesque city of Ghent, Belgium was the site of the 7th International Research Symposium on the Marfan Syndrome, held September 14-17, 2005. An astounding 207 physicians and scientists and over 27 leaders of voluntary health organizations from the International Federation of Marfan Syndrome Organizations attended this meeting. Dr. Anne De Paepe, chair, along with her co-chairs Dr. Peter Byers and Dr. Hal Dietz, the program coordinator Dr. Bart Loeys, and the rest of the Scientific Organizing Committee put together an engaging program designed to promote constructive discussions and vibrant debate on the current understanding of the Marfan syndrome and the controversies that still exist on diagnosis, treatment and pathogenesis of the Marfan syndrome.
The highlights of the symposium included:

1. Clinical diagnosis of Marfan syndrome: how good are the criteria ?

The clinical diagnostic criteria for MFS, defined as the Ghent nosology in 1996, have certainly increased diagnostic accuracy and are still the golden standard for establishment of a clinical diagnosis of Marfan syndrome. However, there are still some instances in which these criteria are difficult to apply. This is especially true in children, as many symptoms will only develop during adulthood and in families with variable clinical presentation. In those cases, the addition of molecular fibrillin-1 studies might add to the diagnostic accuracy. During the meeting it was shown that there is a need for some adjustments of the criteria. For example, the degree of scoliosis does not seem to be that important, so the limit of 20% could be omitted. For the ocular system, myopia should be added as a minor criterion and the other minor criteria should be reconsidered.

2. The role of fibrillin-1 mutation analysis

An overview was given about the international fibrillin-1 mutation database and how this information can be used to help understand the distinction between classic Marfan syndrome and disorders that are also caused by mutations in the fibrillin-1 gene but do not necessarily share the same long-term cardiac risks.
Attention was also paid to the genetics of diseases that belong to the spectrum of Marfan related diseases, such as familial thoracic aortic aneurysm syndrome, congenital contractural arachnodactyly and Weill-Marchesani syndrome. For the latter, the gene for an autosomal recessive form was identified, namely ADAMTS10 but also interesting findings about fibrillin-1 dominant mutations were reported. All these studies may help to reshape the way in which diagnostic criteria are used to predict long term expectations for individuals and their families.

3. Better understanding of the etiology of the Marfan syndrome leads to therapeutic promises

Detailed overview was presented of the research on how mouse models for Marfan syndrome have enabled a greater understanding of the biological mechanisms responsible for the characteristics of the disorder. For a long time, scientists believed that structural deficiency of the fibrillin-1 protein was the most important player in the etiology of Marfan syndrome. Mouse models have now shown that this structural deficiency leads to the activation of another biological pathway, namely the transforming growth factor beta signaling (TGFbeta) pathway. TGFbeta is an important growth factor that is widely present throughout the human body. Activation of this pathway plays a major role in the development of aortic aneurysms in Marfan syndrome patients. Understanding this biological pathway has given scientists not only a better understanding of the formation of aortic aneurysms but also opened new and unexpected targets for drug treatments that may define a new era in which future research will include clinical trials for new drug therapies. At the meeting very promising results from a mouse study with a new medication, called losartan, were shown. Losartan, an angiotensin type 1 receptor blocker, also has an inhibiting effect of the TGFbeta pathway and rescues the aortic growth in Marfan mice. Most importantly this medication has already a widespread use for diseases such as hypertension and heart-failure and as such is ready to be used in Marfan patients. However, randomized large scale trials in Marfan patients are now necessary to confirm the efficacy of this medication in humans before this kind of treatment can be used on a widespread basis.

4. Identification of new Marfan related disease: important implications for management

Exciting progress has also been made in the recognition of a Marfan-related disease, which is now called the Loeys-Dietz syndrome. This disease has some features overlapping with Marfan syndrome but is mainly characterized by the presence of widely spaced eyes (hypertelorism), cleft palate and/or bifid uvula and aortic aneurysms with arterial tortuosity.
Identification of mutations in TGFBR1 and TGFBR2 genes (notably the cell surface receptors for the molecule TGFbeta) has added tremendous insights to our understanding of aortic aneurysms and Marfan syndrome. Other groups have described TGFBR2 mutations in a Marfan-like disorder that resembles Marfan syndrome but results in a clinical picture that is somewhat different (referred to as MFS2). Discussions ensued on how clinical management for these related disorders is different from traditional follow-up for Marfan syndrome. In the Loeys-Dietz syndrome aneurysms do not only occur at the aortic root (as in Marfan syndrome) but throughout the entire arterial tree. As a consequence it is necessary to perform imaging of the arterial tree from head to pelvis. Even more important is the observation of early death and dissections at smaller aortic root diameters than in Marfan syndrome. As such, a more aggressive surgical management in patients with TGFBR mutations is justified, all the more since (preliminary) results on surgical interventions in these patients are good, with no excess in perioperative mortality. This means that surgery at smaller aortic root diameters than in Marfan syndrome is recommended.

5. Clinical management of cardiovascular manifestations in Marfan syndrome

Discussion of clinical management of cardiovascular manifestations and the developments in surgical options for aortic repair highlighted the last day of the meeting. Thanks to improved medical and surgical treatment, the median survival has markedly increased over the past decades. It is obvious that the major determinant of life expectancy in MFS is the progressive dilatation of the proximal aorta, leading to increased risk for rupture and/or dissection. The precise aetiology of this progressive dilatation is not known in detail but it is the result of both weakness of the vessel wall and increased local pressures. The major determinant of the risk for aortic dissection is the diameter of the proximal aorta. Other known risk factors in Marfan syndrome are hypertension, absence of beta-blockade, strenuous exercise, sleep apnoea, pregnancy and aortic stiffness.
At present, beta-blockers remain the cornerstone for cardiovascular treatment in Marfan patients. It has been demonstrated in the 1990's that these agents decrease the progression of aortic dilatation. However, there are some important drawbacks with regard to studies on beta blocking therapy in MFS. There is a wide variabilty in the type and dosis of the beta blockers used in different trials. The study groups are on average very small and heterogeneous. Current alternatives include ACE-inhibitors or calcium channel blockers, but the use of these medications in Marfan syndrome patients has also poorly been studied. The promising results from losartan in the mice studies need to be confirmed in a human trial.
From a surgical perspective, composite graft repair (Bentall procedure) remains the gold standard. The current "conservative" criteria for surgical intervention are =5.5 cm aortic root measurement without moderate or severe aortic regurgitation (AR) or =5.0 cm with AR; =0.4-0.5 cm documented increase in root diameter in =1 year and lower values with family history of dissection at a young age. Over the past decade, several factors have driven towards lower limits for surgery. These include improved techniques and lower mortality of composite graft repair, valve-sparing techniques that avoid need for anti-coagulation and better outcome of valve-sparing surgery at smaller aortic diameters. In specialized centers, valve sparing techniques are a good alternative for composite graft repair. The current "forward-looking" criteria are to operate at root diameters =5.0 cm with little or no AR in order to optimize chances of valve-sparing repair. Patients receiving valve sparing repair of the aortic root should be aware of the risk for re-intervention (10-20% after 15 years).
The use of aortic stents in Marfan patients is limited. Advanced endovascular management options (in MFS) are delicate procedures even for dedicated specialized centers, but they have the potential to reconstruct the dissected aorta in an emergency setting. Stents should be regarded as a temporary solution awaiting conventional graft surgery.

6. Application of the current guidelines in daily practice: how well are the patients served?

The Euro Heart Survey has studied application of guidelines and therapy in patients with congenital heart disease. In this survey, 800 Marfan patients were included. The survey demonstrated that clinical practice is fairly consistent with guidelines for surgical intervention. However, guidelines for imaging of the aorta are followed in only 50-60 % of cases. Every patient with MFS should undergo CT/scan or MRI at least once and in cases with dilatation and/or in postoperative cases, this exam should be repeated on a regular basis. Drug treatment in MFS patients in Europe is close to targets: almost 80% of patients are on beta-blocking therapy.

In the closing session, Dr. Peter Byers summed up by saying that it was a watershed meeting occurring at a time of tremendous research activity which not only created new insights on how fibrillin gene mutations produced each of the different aspects of Marfan syndrome but also identified new biological pathways that were targets for drug intervention with potentially dramatic and long-lasting effects. He thought that this was a critical time for research in Marfan syndrome and that the meeting created the cooperative environment in which new approaches would benefit the Marfan community and at the same time advance the scientific understanding of Marfan syndrome.

Along with the scientists came an enthusiastic group of leaders of volunteer Marfan groups from around the world. Over 25 participants of the International Federation of Marfan Syndrome Organizations came to the meeting to get state-of-the-art information. The group came together on the last evening to have a wonderful dinner and meeting where elections were held and many new and familiar faces had time to discuss the opportunities to collaborate and share ideas for their common causes. Priscilla Ciccariello, president of IFMSO was re-elected and several vice-chairs have come forward to pitch in to make this organization grow and share global ideas. Priscilla also celebrated her eightieth birthday and was presented with a beautiful crystal heart. Finally, Dr Anne De Paepe also honored the everlasting efforts from Yvonne Yousten, president of the Association Belge du Syndrome de Marfan and dedicated the meeting to her deceased son, Patrick. In his memory, Yvonne was thanked for her involvement in organizing this meeting.


IFMSO
C/O National Marfan Foundation
22 Manhassett Avenue
Port Washington, NY 11050
http://www.marfanworld.org

Contact Information
President
Priscilla Ciccariello cilla71@aol.com
Vice Presidents:
Wenche Snekkevik, (Norway),
Justin Nix, (Australia),
Yoko Shimozaki, (Japan)
Pernille Mai Strauss Warren, (Denmark)

Treasurer - Cheryl Williams, United States:
research@marfan.org
Webmaster
Peter Ciccariello
cgi77@aol.com

E-mail news from IFMSO members:

Victoria, Australia


An e-mail from Sally Ferguson provided news about Justin Nix, one of the four IFMSO Vice Presidents, recently elected at the IFMSO meeting in Ghent, Belgium: "Just a note to let you know that Justin is in hospital. He was feeling unwell on Wednesday and went into hospital on Thursday night. I spoke to him this morning (Saturday Oz time) and again this evening. He is sounding much better than yesterday when he was in the emergency ward. His temperature has been fluctuating with bouts of uncomfortable pulpitations and ill feelings and he is on a drip. The doctors suspect he may have endocarditis. He has the characteristic "splinters" showing under his fingernails. They are running blood and culture tests and will know more in the morning. They will also do a transoesophageal echo tomorrow. I expect they will be keeping him in hospital for some time. Despite everything he sounded in good spirit.
GOOD NEWS UPDATE: "Justin left the hospital this morning with the good news that he infection he has is not endocarditis. He will receive home care with daily visiting nurses. "

Sally Ferguson, President
Marfan Association Victoria Inc.


Japan

Yoko Shimozaki, IFMSO Vice President, has updated us on some recent activies of the Marfan Network Japan:
"Thank you for your showing interest in our activity in Japan. Let me tell you more detail .
The things started with our guidebook for Marfan syndrome we made last year. A young cardiologist named Shigekiyo Takahashi is a medical doctor of Kizawa Memorial Hospital in Gifu Prefecture where Masayo(the founder
of MNJ) was taken at her first aortic dissctiton ten years ago. There she was not diagnosed to have Marfan syndrome and they could not find her dissection either. Dr. Takahashi was not there of course ten years ago but he felt some kind of responsibility after reading the guide book which was sent by Masayo's parents to the hospital. So he decided
to have an occasion to let the emergency staff and staff of the hospital know about Marfan syndrome. There were three speakers on that day (28th of Nov.). The first one is of course Dr. Takahashi who talked about Marfan syndrome and its characteristics. Then Masayo's husband talked about the importance of emergency situation and lastly I talked about my own experience as the affected and our organizational activity. I showed them several photoes from Baltimore and Ghent too. The number in audience was about 80, though we did not expect so many in advance in such a local town. The event was successful and many said they had not known about Marfan syndrome before. Dr. Takahashi said "This is just a first step for us". We will continue to follow-up on this meeting.
Yours, Yoko Shimozaki."
Marfan Network Japan

Mexico

We received this informative and interesting e-mail from Geraldine (Mexico) on December 13th, 2005:
Dear IFMSO members,
I hope this letter finds everyone well. It's been a letter long in the waiting but with the busy lives we all lead, it has become a luxury indeed. Life in this fast-paced city of ours is sometimes a little less than a nightmare. I still work full time as the Directory of language Studies at the Universidad of the Americas here in Mexico City and manage to preside over Marfan de Mexico, A.C. The association has grown and we are happy but we feel that the culture still has some way to go with the acceptance of being different. That attitude has changed considerably since we began but nonetheless still leaves room for improvement.

Going back to our beginnings, our story has been a process of patience, perseverance, and persistence as I'm certain many have experienced. We began as a contact - support group and were lucky to attend the Marfan Conference in San Francisco, in November, 1992. Now that was exciting if you recall. We represented seven countries and signed the first papers for the World Federation. In 1998, we were legally recognized by the Mexican government making us the only Spanish - speaking association in the world. As there was no material available in Spanish for the general public at the time, we had the enormous job just in translating medical information. Shortly after this, Cuba became the second Spanish-speaking association. They, also, began the tremendous job of spreading information about Marfan in Cuba.

Our web page currently under construction first appeared in 1998. We were so swamped with enquires from around the Spanish-speaking world that we consequently wrote to different countries encouraging them to begin their own associations in their respective countries. Fortunately, countries like Spain, Argentina, Chile and Peru started their own associations and have been growing.

During the years, we have published a number of brochures about the condition. With the permission of Dr. Reed Pyeritz and Cheryll Gasner, R.N., we were able translate their booklet The Marfan Syndrome making it the first edition in Spanish in October, 2003. Also, thanks to one of our TV stations, we were able to produce a video on the condition. In February, 2004, a wonderful book for youth was written and published. All of this material was shared and sent to our fellow Spanish -speaking Marfan groups.

In Mexico, medical investigation on Marfan especially in the National Institute of Cardiologia Ignacio Chavez had presented a number of important publications in those early years and continues to this day. In 1996, the multidisciplinary team of researchers under the lead of Dr. Carlos Pineda at this institute presented their work in Belgium:

The Musculoskeletal Manifestations of Marfan Syndrome (MFS). Its Frequency and Coexpression.

In 1998, they published their work:

Revised Diagnostic Criteria for the Marfan Syndrome - A Clinical Radiographic Essay.

This was only the beginning and this year alone 2005, they produced important findings for three papers. Those, we scanned and will send them to you under attachment in separate letters. Dr. Carlos Pineda was awarded Honorable Mention for his work in Marfan by the Mexican Rheumatology Association early this year.

Mexico and Canada will hold a first joint Rheumatology congress in Acapulco in February, 2006 in which Mexico will present their project:

The Relationship between Coxa Valga and the Major Diagnostic Criteria for the Marfan Syndrome

We have asked for permission to set up an information stand on Marfan at this Congress.

In addition, we have had a specialized clinic for Marfan patients under the care of a multidisciplinary medical team at the above mentioned institute since the mid nineties.

And that is our story. It's been a challenging undertaking. But, it is only with a united front that we can move toward finding a cure for this condition. Hopefully, another dream some day, we will be able to have a conference for all Spanish-speaking Marfan associations in the world.

Con mucho corazon,
and warm wishes,
Geraldine


Spain

We had a nice "Best regards," e-mail from Nicolas Beltran Sogorb, (Presidente de SIMA), who is doing a great job in the Marfan organization in Spain. (SIMA Asociación de Afectados Síndrome de Marfan.) You can contact him at his e-mail: info@marfansima.org, or SIMA web site: www.marfansima.org Check out his web site when you have a chance. (You can use the IFMSO links to the different IFMSO organizations, if you wish: http://www.marfanworld.org )
Please send an e-mail with your organizational activities for the next issue of Marfanworld E-News to:
Priscilla Ciccariello
, President
Peter Ciccariello, Webmaster

IFMSO membership information and forms are available on the IFMSO Official Website at MARFANWORLD.COM

Copyright 2005 International Federation of Marfan Syndrome Organizations