Our son Aurélien, born in 2015, suffers from a spontaneous form of Marfan syndrome diagnosed during his first year of life.
Marfan syndrome results from connective tissue damage[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 under- or misproduced, and therefore fails to assume its proper role in the organisms of affected individuals.
This fibrillin malfunction normally has consequences for the entire organism of those affected, and is generally expressed at the skeletal, pulmonary, ocular and, above all, cardiovascular levels.
[2]
which requires ongoing and often costly treatment. In most cases, this involves major surgery on the aorta (often combined with surgery on the aortic valve).
However, even within the same family with an identical mutation, the intensity of damage varies widely. As a result, some people affected by the syndrome have little impairment.
[3]
while at the other end of the spectrum, the life expectancy of some neonatal Marfans is very limited
[4]
. Between these two extremes, we find the majority of Marfans whose disease sometimes severely handicaps them, and who must regularly check the dilation of their aorta.
In the current state of scientific knowledge, this great variability in damage and intensity is not yet well understood (apart from certain leads relating in particular to: the position of deleterious mutations on certain exons[5] the types of consequences of deleterious mutations[6] and the gender of patients[7]).
It was against this backdrop that we decided to set up a Foundation to support scientific research. The Foundation’s first innovative project is to provide interested researchers with a tool in the form of a computer platform containing a cross-referenced genomic/phenotypic database of a cohort of 101 Marfan syndrome patients, with a view to gaining a better understanding of the variability and intensity of the disease using the most advanced technological means available.
The purpose of the Foundation is to serve as a vehicle for raising the funds needed to develop and manage this bioinformatics tool.
Ludivine Verboogen & Romain Alderweireldt
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[1] Extra-cellular tissue holding together the cells that make up the human body. See the page dedicated to Marfan syndrome on the orphanet website.
[2] Dietz H., ” Marfan Syndrome ” in
GeneReviews
April 18, 2001, last updated February 2, 2017, available at : https: //www.ncbi.nlm.nih.gov/books/NBK1335/.
[3] And, in exceptional cases, even lead careers as top sportsmen and women, such as :
Flo Hyman
captain of the silver-medal-winning U.S. volleyball team at the 1984 Olympic Games ;
Isaiah Austin
a professional basketball player currently playing in the Chinese league, whose NBA career was cut short following the diagnosis of his illness ;- Like that of
Jonathan Jeanne
whose career was also cut short just outside the NBA when he was diagnosed with Marfan.
Apart from these athletes whose Marfan diagnosis has been confirmed, the physical characteristics of Michael Phelps have led some observers to put forward the – as yet unconfirmed – hypothesis that the most successful athlete in the history of the modern Olympic Games is also affected by Marfan syndrome or another connective tissue disorder: http: //www.raredr.com/news/michael-phelps-marfan.
[4] And would average around 16 months for neonatal Marfan 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 replaced 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
, April 30, 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 ResearchMarch 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 VesselsJanuary 2016, DOI: 10.1007/s00380-016-0793-2.
[6] ” Haploinsuffiency “or Dominant Negative “see for example : Landis BJ. et al, ” Genotype-phenotype correlations in Marfan syndrome ” in
Heart Online First
, published on June 8, 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
Circ 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.