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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

(2009) PEDIATRICS. 123(1). p.391-398
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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.
Keywords
Marfan syndrome, FBN1, childhood, international criteria, CARDIOVASCULAR MANIFESTATIONS, MENTAL-RETARDATION, NATURAL-HISTORY, CHILDHOOD, FIBRILLIN-1, PREVALENCE, DISORDERS, DIAGNOSIS, PHENOTYPE, CRITERIA

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Chicago
Faivre, Laurence, Alice Masurel-Paulet, Gwenaëlle Collod-Béroud, Bert Callewaert, Anne H Child, Chantal Stheneur, Christine Binquet, et al. 2009. “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.” Pediatrics 123 (1): 391–398.
APA
Faivre, Laurence, Masurel-Paulet, A., Collod-Béroud, G., Callewaert, B., Child, A. H., Stheneur, C., Binquet, C., et al. (2009). 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. PEDIATRICS, 123(1), 391–398.
Vancouver
1.
Faivre L, Masurel-Paulet A, Collod-Béroud G, Callewaert B, Child AH, Stheneur C, et al. 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. PEDIATRICS. 2009;123(1):391–8.
MLA
Faivre, Laurence, Alice Masurel-Paulet, Gwenaëlle Collod-Béroud, et al. “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.” PEDIATRICS 123.1 (2009): 391–398. Print.
@article{516111,
  abstract     = {From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients {\textlangle}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 {\textlangle}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.},
  author       = {Faivre, Laurence and Masurel-Paulet, Alice and Collod-B{\'e}roud, Gwena{\"e}lle and Callewaert, Bert and Child, Anne H and Stheneur, Chantal and Binquet, Christine and Gautier, Elodie and Chevallier, Bertrand and Huet, Fr{\'e}d{\'e}ric and Loeys, Bart and Arbustini, Eloisa and Mayer, Karin and Arslan-Kirchner, Mine and Kiotsekoglou, Anatoli and Comeglio, Paola and Grasso, Maurizia and Halliday, Dorothy J and B{\'e}roud, Christophe and Bonithon-Kopp, Claire and Claustres, Mireille and Robinson, Peter and Ad{\`e}s, Lesley and De Backer, Julie and Coucke, Paul and Francke, Uta and De Paepe, Anne and Boileau, Catherine and Jondeau, Guillaume},
  issn         = {0031-4005},
  journal      = {PEDIATRICS},
  keyword      = {Marfan syndrome,FBN1,childhood,international criteria,CARDIOVASCULAR MANIFESTATIONS,MENTAL-RETARDATION,NATURAL-HISTORY,CHILDHOOD,FIBRILLIN-1,PREVALENCE,DISORDERS,DIAGNOSIS,PHENOTYPE,CRITERIA},
  language     = {eng},
  number       = {1},
  pages        = {391--398},
  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},
  url          = {http://dx.doi.org/10.1542/peds.2008-0703},
  volume       = {123},
  year         = {2009},
}

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