Our son Sam was born on September 24th, 2017. He is suffering from neonatal Marfan syndrome, a serious variant of Marfan syndrome. Marfan syndrome is an evolutionary disorder in which the connective tissue of the body is not produced properly. This mainly affects the heart, lungs, skeleton and eyes. There is currently no causal treatment for Marfan syndrome. Infants with neonatal Marfan syndrome have low life expectancy. The doctors gave Sam a maximum life expectancy of 2 years at birth.
Marfan syndrome is a genetic disorder that affects about one person in 5,000. In three out of four people, Marfan's Syndrome was transmitted genetically within the family. In one person in four, it results from a spontaneous new mutation. Neonatal Marfan is always " de novo ", as at Sam's.
Marfan syndrome is caused by a mutation of the FBN1 gene (Marfan gene), so that the protein fibrillin-1, and thus connective tissue, is not produced adequately or properly in the organism.
We started a blog " Lieve Sam » and through our blog, we came into contact with the parents of Aurélien, a small Belgian boy of 2 and a half years with neonatal Marfan syndrome.
His parents, Romain Alderweireldt and Ludivine Verboogen, launched an important innovative research project on rare diseases in Belgium via their " Fondation 101 Génomes ».
The objective of the pilot project of this Foundation, the " Project 101 genomes Marfan ", is to create a genetic and clinical database from 101 patients with Marfan syndrome. Through this database, scientists from various specialties will be able to do some new research on this rare connective tissue disorder.
Why this search?
Until now, neonatal Marfan was thought to be a predictable disease caused by this "Marfan gene" and that all children with neonatal Marfan would die within two years.
In recent years, scientists have found that there are more variations between patients in terms of the evolution and severity of the disease than originally thought. Part of this variation can be explained by early diagnosis and better symptomatic treatments, but also indicates that there are natural variations. Currently, neonatal Marfan syndrome is considered to be the most severe form of Marfan syndrome.
Similarly, in classical Marfan syndrome, it appears that there are many variations between patients and that even within the same family (in which all patients carry the same genetic mutation FBN1), there may be large Differences. Some people with Marfan syndrome have few symptoms and live very old, others die very young.
This platform would allow scientists to further study this variability in order to understand if other genetic factors, besides the Marfan gene, lead to it and what are they.
Concept of the study
The objective of this research is to develop a database of 101 patients with Marfan syndrome and to conduct research on all their genetic material. Whereas so far only the Marfan gene has always been studied, the objective of this project is precisely to map all the genes of these patients.
By linking all the genetic information of patients to their syndrome and comparing them, scientists can determine if there are other genes, in addition to the Marfan gene, that influence the development of the syndrome. And if there are other genes that also have an effect on the evolution of the syndrome and that can possibly explain why this disease manifests very slightly in some patients and very seriously in others.
The mapping, not only of the Marfan gene, but also of all the genes of the Marfans patients, thus makes this research innovative and is an important complement to the already existing knowledge about Marfan syndrome.
If, by comparing Marfan patients, there are recurrences and similarities that show that other hitherto unknown genes affect Marfan's syndrome, it may be possible to intervene and develop strategies that can improve the effect genes that have a positive influence or mitigate the effect of genes that have a negative influence. On this basis, other treatments or medications can be developed in the future, which can improve patient health.
To set up their Fondation 101 Génomes , Aurélien's parents won the Edelweiss 2018 Award from RaDiOrg for their contribution to rare diseases in Belgium.
Why was this research not done before?
Since Marfan's syndrome is a rare disease and the neonatal Marfan is even rarer, so far, little is known about the great variability that exists between patient attacks. Recent research shows that there is also a great variability between children with neonatal Marfan. This new perspective makes it possible and relevant an innovative research.
In addition, the technique necessary to "read" the whole range of genes of a patient (the whole genome) and compare it with other patients was still inaccessible until recently.
Currently, thanks to the latest scientific developments, it is perfectly possible to carry out this research at an affordable price.
What do we need?
Two things are needed to carry out this research. First, a cohort of at least 101 patients with Marfan syndrome, with a number of different FBN1 mutations and a net variability in the severity of the disease. This will allow a genetic comparison between patients with mild and severe Marfan syndromes.
Secondly, an amount of 500,000,-euros is required for 2018 in order to be able to set up and carry out the research. Part of this amount has already been collected.
This project is carried out by the Fondation 101 Génomes , created by Aurélien's parents, in collaboration with the King Baudouin Foundation of Belgium. A large number of scientists and national and international organizations working in the field of Marfan have already pledged to support and cooperate in this project.
Laurens Ivens and Dessie Lividikou
Amsterdam April 2018
Our blog Lieve Sam www.lievesam.weebly.com
More information about the project 101 genomes Marfan can be found on http://www.f101g.org/
Professor Bart Loeys, University of Antwerp:
« It is very inspiring to see how much Sam and Aurélien's parents are involved in scientific research for a better treatment of Marfan syndrome. Their inexhaustible energy and unbridled commitment encourage us to look for even more missing pieces of the puzzle. The "natural" variability in the severity of clinical signs in Marfan patients carrying the same genetic mutation on the FBN1 gene tells us that nature itself is finding ways to compensate at least partially for the effect of the genetic mutation. If we can find out how "mother nature" does this, we can try to find treatment methods that produce the same effect. Genetics has undergone a real technological revolution in recent years, and the time has come to use this technology to discover genetic explanations for clinical variations among Marfan patients. I am happy and proud to be able to contribute to this national and international cooperation between scientists, patients and their parents. »
Professor Julie de backer, University of Ghent:
« The chances of collaborating concretely with patients and families in the context of research are generally low – in General, this does not go beyond the inclusion of patients in the study protocols. The opportunity offered by Romain and Ludivine is unique and allows us to develop very concrete questions from the point of view of patients. All they have learned about the syndrome in such a short time is unheard of and, on that basis, they have developed a solid project.
The question of what attracts us so much in research is often asked – although the answer to this question is obvious: disorders such as Marfan's syndrome are often accompanied by serious (sometimes fatal) problems – it is very difficult to bear for patients and their families in the first place and even as a doctor, this does not leave indifferent. By actively participating in research, we try (small steps) to relieve this suffering and it gives us the energy to continue our work. »
 It is a question of linking all genomic data of these patients to their phenotypic characteristics.
 Not only the specific gene of Marfan, but also the entire genome of these patients.
 This approach is based on the Genome-wide Association study (GWAS).
 Rare disease organization