Our son Aurélien, born in 2015, is suffering from a spontaneous form of Marfan syndrome diagnosed during his first year of life.

Marfan syndrome is the result of an injury to connective tissues^[1] caused by a deleterious mutation of the FBN1 gene on chromosome 15, with the result that the fibrillin protein encoded by this gene is not sufficiently or incorrectly produced and therefore does not correctly assume its role in the organisms of affected individuals.

This misfunction of the Fibrillin has, normally, consequences on the whole organism of the people affected and is expressed, generally, at the level skeletal, pulmonary, ocular and especially cardio-vascular^[2] This leads to ongoing and often extensive treatment. In most cases, this treatment involves major surgery on the aorta (often combined with surgery on the aortic valve).

However, even within the same family with identical mutations, the intensity of the attacks is very variable. Some people affected by the syndrome have little^[3] while at the other end of the spectrum, the life expectancy of some neonatal Marfans is very limited...^[4]. Between these two extremities, we find the majority of the Marfans that the disease sometimes handicaps heavily and which must regularly control the dilation of their aorta.

In the current state of scientific knowledge, this great variability of infringements and their intensity is not yet well understood (aside from certain relevant leads, in particular: to the position of deleterious mutations on certain exons^[5] types of consequences of deleterious mutations^[6] and gender of patients^[7]).

It is in this context that we have decided to set up a foundation for the purpose of supporting scientific research. The first unpublished project of this foundation is to make available to interested researchers a tool in the form of a computer platform containing a genome/phenotypic cross-database of a cohort of 101 patients with of Marfan syndrome in order to better understand the variability and intensity of the attacks using the most advanced technological means.

The purpose of this foundation is to serve as a vehicle to raise the necessary funds in particular to finance the development and management of this bioinformatics tool.

Ludivine Verboogen and Romain Alderweireldt

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[1]  The extra-cellular tissues that hold together the cells that make up the human body. See the page dedicated to Marfan syndrome on the Orphanet site.

[2] Dietz H., " Marfan Syndrome "in GeneReviews18 April 2001, last updated 2 February 2017, available at https://www.ncbi.nlm.nih.gov/books/NBK1335/.

[3]  In exceptional cases, they even lead careers as top sportsmen and women, for example:

• the captain of the silver medal-winning US volleyball team at the 1984 Olympic Games;
• Isaiah Austin, a professional basketball player currently playing in the Chinese championship, whose career in the NBA was interrupted as a result of the diagnosis of his illness;
• Like the one in James Jane whose career was also cut short at the NBA gates when he was diagnosed with Marfan.

Apart from those athletes with a confirmed Marfan diagnosis, the physical characteristics of Michael Phelps has led some observers to speculate - unconfirmed at present - that the most successful athlete in the history of the modern Olympic Games may also be affected by Marfan's syndrome or some other connective tissue disorder: http://www.raredr.com/news/michael-phelps-marfan.

[4]  And would be on average around 16 months for neonatal or more precisely rapid onset Marfan". Early onset » : « Marfan syndrome (MFS) (OMIM 154700) is an autosomal dominant disorder of fibrous connective tissue involving the ocular, skeletal, and cardiovascular systems. MFS patients present with clinical variability, in which the rare neonatal Marfan syndrome (nMFS) has the most severe presentation in early childhood. The prognosis of nMFS is very poor, with a mean survival age of only 16.3 months. Valvular insufficiencies and diaphragmatic hernias have been associated with shorter survival in patients diagnosed before the age of 1 year. […] The term neonatal Marfan syndrome was first used in 1991 to describe the most severe phenotype of MFS similar to cases previously known as infantile Marfan syndrome, congenital Marfan syndrome, and severe perinatal Marfan syndrome. Recently, it has been suggested that the term neonatal MFS should be placed by early onset and rapidly progressive MFS to represent the most severe features of MFS in early childhood "in Peng Q. et al, " A novel Fibrillin-1 gene missense mutation associated with neonatal Marfan syndrome: A case report and review of the mutation spectrum », BMC Pediatrics, 30 April 2016, 16:60, DOI 10.1186/s12887-016-0598-6.

See also « Lessons From A Little Fighter – Felix Reeves "by Sheena Reeves.

[5]   « Most previously identified NMFS-associated FBN1 mutations are known to cluster between exons 24 and 32, which is the neonatal region of FBN1 "in Peng Q. et al, " A novel Fibrillin-1 gene missense mutation associated with neonatal Marfan syndrome: A case report and review of the mutation spectrum "in BMC Pediatrics, 30 Apr 2016, 16:60, DOI 10.1186/s12887-016-0598-6.

See also: Stheneur C. et al, " Prognosis factors in Probands With an FBN1 Mutation diagnosed before the Age of 1 year "in Pediatric Research, March 2011, DOI: 10.1203/PDR.0b013e3182097219 and ; Maeda J. et al, " Variable severity of cardiovascular phenotypes in patients with an early-onset form of Marfan syndrome harboring FBN1 mutations in exons 24 – 32 "in Heart and vessels, January 2016, DOI: 10.1007/s00380-016-0793-2.

[6]  "Haploinsufficiency "or" dominating Negative "See for example: Landis BJ. et al, " Genotype-phenotype correlations in Marfan syndrome "in Heart Online First, published on 8 June 2017 as 10.1136/heartjnl-2017-311513 and; Franken R. et al., " Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome "in IARC Cardiovasc Genet, April 2015, DOI: 10.1161/CIRCGENETICS. 114.000950.

[7] Renard M. et al, " Sex, pregnancy and aortic disease in Marfan syndrome "in PLoS ONE, July 2017, https://doi.org/10.1371/journal.pone.0181166.