Abstract：
The primary aim was to gain insight into the growth of the aortic root in children and young adults with Marfan syndrome (MFS). Furthermore, we aimed to identify a clinical profile of patients with MFS who require an aortic root replacement at a young age with specific interest in age, sex, height and fibrillin-1 (FBN1) genotype.
Aortic root dimensions of 97 patients with MFS between 0 year and 20 years and 30 controls were serially assessed with echocardiography. Trends were analysed using a linear mixed-effect model. Additionally, including only patients with MFS, we allowed trends to differ by sex, aortic root replacement and type of FBN1 mutation.
Average aortic root dilatation in patients with MFS became more pronounced after the age of 8 years. In the MFS cohort, male patients had a significantly greater aortic root diameter than female patients, which was in close relationship with patient height. There was no difference in aortic root growth between children with dominant negative (DN) or haploinsufficient FBN1 mutations. However, DN-FBN1 variants resulting in loss of cysteine content were associated with a more severe phenotype. Eleven children needed an aortic root replacement. Compared with patients with MFS without aortic root surgery, these children had a significantly larger aortic root diameter from an early age.
This study provides clinically useful longitudinal growth charts on aortic root growth in children and young adults with MFS. Children requiring prophylactic aortic root replacement during childhood can be identified at a young age. Our growth charts can help clinicians in decision making with regard to follow-up and prophylactic therapy. Loss of cysteine content in the FBN1 protein was associated with larger aortic root dimensions.
Aortic root dimensions of 97 patients with MFS between 0 year and 20 years and 30 controls were serially assessed with echocardiography. Trends were analysed using a linear mixed-effect model. Additionally, including only patients with MFS, we allowed trends to differ by sex, aortic root replacement and type of FBN1 mutation.
Average aortic root dilatation in patients with MFS became more pronounced after the age of 8 years. In the MFS cohort, male patients had a significantly greater aortic root diameter than female patients, which was in close relationship with patient height. There was no difference in aortic root growth between children with dominant negative (DN) or haploinsufficient FBN1 mutations. However, DN-FBN1 variants resulting in loss of cysteine content were associated with a more severe phenotype. Eleven children needed an aortic root replacement. Compared with patients with MFS without aortic root surgery, these children had a significantly larger aortic root diameter from an early age.
This study provides clinically useful longitudinal growth charts on aortic root growth in children and young adults with MFS. Children requiring prophylactic aortic root replacement during childhood can be identified at a young age. Our growth charts can help clinicians in decision making with regard to follow-up and prophylactic therapy. Loss of cysteine content in the FBN1 protein was associated with larger aortic root dimensions.
摘要：
目的：主要目的是了解患有马凡氏综合征（MFS）的儿童和年轻人的主动脉根部生长。此外，我们的目的是确定MFS患者的临床特征，这些患者在年轻时需要进行主动脉根部置换，并且对年龄有特殊兴趣。性别,身高和原纤维蛋白-1（FBN1）基因型。
方法：用超声心动图连续评估了97例0年至20年之间的MFS患者和30例对照的主动脉根部尺寸。使用线性混合效应模型分析了趋势。此外,仅包括MFS患者，我们允许趋势因性别而异，主动脉根置换和FBN1突变类型。
结果：MFS患者的平均主动脉根部扩张在8岁后变得更加明显。在MFS队列中，男性患者的主动脉根部直径明显大于女性患者，这与患者身高密切相关。显性阴性（DN）或单倍体不足的FBN1突变的儿童之间的主动脉根部生长没有差异。然而,导致半胱氨酸含量损失的DN-FBN1变体与更严重的表型相关。11名儿童需要进行主动脉根部置换。与无主动脉根部手术的MFS患者相比，这些儿童从小就有明显较大的主动脉根部直径.
结论：本研究提供了MFS儿童和年轻成人主动脉根部生长的临床有用纵向生长图。在儿童时期需要预防性主动脉根部置换的儿童可以在年轻时被识别。我们的增长图可以帮助临床医生在后续和预防性治疗方面做出决策。FBN1蛋白中半胱氨酸含量的损失与较大的主动脉根尺寸有关。
方法：用超声心动图连续评估了97例0年至20年之间的MFS患者和30例对照的主动脉根部尺寸。使用线性混合效应模型分析了趋势。此外,仅包括MFS患者，我们允许趋势因性别而异，主动脉根置换和FBN1突变类型。
结果：MFS患者的平均主动脉根部扩张在8岁后变得更加明显。在MFS队列中，男性患者的主动脉根部直径明显大于女性患者，这与患者身高密切相关。显性阴性（DN）或单倍体不足的FBN1突变的儿童之间的主动脉根部生长没有差异。然而,导致半胱氨酸含量损失的DN-FBN1变体与更严重的表型相关。11名儿童需要进行主动脉根部置换。与无主动脉根部手术的MFS患者相比，这些儿童从小就有明显较大的主动脉根部直径.
结论：本研究提供了MFS儿童和年轻成人主动脉根部生长的临床有用纵向生长图。在儿童时期需要预防性主动脉根部置换的儿童可以在年轻时被识别。我们的增长图可以帮助临床医生在后续和预防性治疗方面做出决策。FBN1蛋白中半胱氨酸含量的损失与较大的主动脉根尺寸有关。
