title: Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations.
abstract: From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients <18 years of age at the last follow-up evaluation were analyzed (32%). At the time of diagnosis, the median age was 6.5 years. At the last examination, the population was classified as follows: neonatal Marfan syndrome, 14%; severe Marfan syndrome, 19%; classic Marfan syndrome, 32%; probable Marfan syndrome, 35%. Seventy-one percent had ascending aortic dilation, 55% ectopia lentis, and 28% major skeletal system involvement. Even when aortic complications existed in childhood, the rates of aortic surgery and aortic dissection remained low (5% and 1%, respectively). Some diagnostic features (major skeletal system involvement, striae, dural ectasia, and family history) were more frequent in the 10- to <18-year age group, whereas others (ascending aortic dilation and mitral abnormalities) were more frequent in the population with neonatal Marfan syndrome. Only 56% of children could be classified as having Marfan syndrome, according to international criteria, at their last follow-up evaluation when the presence of a FBN1 mutation was not considered as a major feature, with increasing frequency in the older age groups. Eighty-five percent of child probands fulfilled international criteria after molecular studies, which indicates that the discovery of a FBN1 mutation can be a valuable diagnostic aid in uncertain cases. The distributions of mutation types and locations in this pediatric series revealed large proportions of probands carrying mutations located in exons 24 to 32 (33%) and in-frame mutations (75%). Apart from lethal neonatal Marfan syndrome, we confirm that the majority of clinical manifestations of Marfan syndrome increase with age, which emphasizes the poor applicability of the international criteria to this diagnosis in childhood and the need for follow-up monitoring in cases of clinical suspicion of Marfan syndrome.
authors.affiliation: Genetic Center, Centre Hospitalier Universitaire Dijon, Dijon, France. laurence.faivre@chu-dijon.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Collod-Béroud
authors.forename: Bert L
authors.initials: BL
authors.lastname: Callewaert
authors.forename: Anne H
authors.initials: AH
authors.lastname: Child
authors.forename: Chantal
authors.initials: C
authors.lastname: Stheneur
authors.forename: Christine
authors.initials: C
authors.lastname: Binquet
authors.forename: Elodie
authors.initials: E
authors.lastname: Gautier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Chevallier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Bart L
authors.initials: BL
authors.lastname: Loeys
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Karin
authors.initials: K
authors.lastname: Mayer
authors.forename: Mine
authors.initials: M
authors.lastname: Arslan-Kirchner
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kiotsekoglou
authors.forename: Paolo
authors.initials: P
authors.lastname: Comeglio
authors.forename: Maurizia
authors.initials: M
authors.lastname: Grasso
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Halliday
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Claire
authors.initials: C
authors.lastname: Bonithon-Kopp
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.forename: Lesley
authors.initials: L
authors.lastname: Adès
authors.forename: Julie
authors.initials: J
authors.lastname: De Backer
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods / Q000639:trends; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines