Faivre Laurence, Masurel-Paulet Alice, Collod-Béroud Gwenaëlle, Callewaert Bert L, Child Anne H, Stheneur Chantal, Binquet Christine, Gautier Elodie, Chevallier Bertrand, Huet Frédéric, Loeys Bart L, Arbustini Eloisa, Mayer Karin, Arslan-Kirchner Mine, Kiotsekoglou Anatoli, Comeglio Paolo, Grasso Maurizia, Halliday Dorothy J, Béroud Christophe, Bonithon-Kopp Claire, Claustres Mireille, Robinson Peter N, Adès Lesley, De Backer Julie, Coucke Paul, Francke Uta, De Paepe Anne, Boileau Catherine, Jondeau Guillaume
Genetic Center, Centre Hospitalier Universitaire Dijon, Dijon, France.
Pediatrics. 2009 Jan;123(1):391-8. doi: 10.1542/peds.2008-0703.
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.
在1009例携带致病性FBN1突变的先证者的大量队列研究中，分析了最后一次随访评估时年龄小于18岁的320例患者的数据（32%）。诊断时的中位年龄为6.5岁。在最后一次检查时，该人群分类如下：新生儿型马凡综合征，14%；重度马凡综合征，19%；经典型马凡综合征，32%；可能的马凡综合征，35%。71%有升主动脉扩张，55%有晶状体异位，28%有主要骨骼系统受累。即使儿童期存在主动脉并发症，主动脉手术和主动脉夹层的发生率仍然较低（分别为5%和1%）。一些诊断特征（主要骨骼系统受累、皮肤条纹、硬脊膜扩张和家族史）在10至18岁年龄组中更常见，而其他特征（升主动脉扩张和二尖瓣异常）在新生儿型马凡综合征患者中更常见。在最后一次随访评估时，若不将FBN1突变的存在视为主要特征，根据国际标准，只有56%的儿童可被归类为患有马凡综合征，且在年龄较大的组中频率增加。85%的儿童先证者在分子研究后符合国际标准，这表明发现FBN1突变在不确定病例中可能是一种有价值的诊断辅助手段。该儿科队列研究中突变类型和位置的分布显示，很大比例的先证者携带位于外显子24至32的突变（33%）和框内突变（75%）。除了致死性新生儿型马凡综合征外，我们证实马凡综合征的大多数临床表现随年龄增加，这强调了国际标准在儿童期该诊断中的适用性较差，以及临床怀疑马凡综合征时进行随访监测的必要性。
