Prognosis factors in probands with an FBN1 mutation diagnosed before the age of 1 year.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder. Diagnostic criteria of neonatal MFS (nMFS), the most severe form, are still debated. The aim of our study was to search for clinical and molecular prognostic factors that could be associated with length of survival. Probands ascertained via the framework of the Universal Marfan database-FBN1, diagnosed before the age of 1 y and presenting with cardiovascular features (aortic root dilatation or valvular insufficiency) were included in this study. Clinical and molecular data were correlated to survival. Among the 60 individuals, 38 had died, 82% died before the age of 1 y, mostly because of congestive heart failure. Three probands reached adulthood. Valvular insufficiencies and diaphragmatic hernia were predictive of shorter life expectancy. Two FBN1 mutations were found outside of the exon 24-32 region (in exons 4 and 21). Mutations in exons 25-26 were overrepresented and were associated with shorter survival (p = 0.03). We report the largest genotyped series of probands with MFS diagnosed before 1 y of life. In this population, factors significantly associated with shorter survival are presence of valvular insufficiencies or diaphragmatic hernia in addition to a mutation in exons 25 or 26.
Service de Pédiatrie, Hôpital Ambroise Paré, Boulogne, 92100 France. chantal.stheneur@apr.aphp.fr
Chantal
C
Stheneur
Laurence
L
Faivre
Gwenaëlle
G
Collod-Béroud
Elodie
E
Gautier
Christine
C
Binquet
Claire
C
Bonithon-Kopp
Mireille
M
Claustres
Anne H
AH
Child
Eloisa
E
Arbustini
Lesley C
LC
Adès
Uta
U
Francke
Karin
K
Mayer
Mine
M
Arslan-Kirchner
Anne
A
De Paepe
Bertrand
B
Chevallier
Damien
D
Bonnet
Guillaume
G
Jondeau
Catherine
C
Boileau
D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D011379:Prognosis; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines