早发性马凡氏综合征(eoMFS)进展迅速,从新生儿期开始,导致严重的临床疾病,预后不良.与eoMFS相关的遗传异常位于原纤维蛋白-1(FBN1)基因外显子25-26中所谓的关键新生儿区域。一名女性新生儿在妊娠37周时因胎儿窘迫伴心动过缓行紧急剖宫产术。紫癜,也没有自主呼吸.在检查中,病人有多处肌肉骨骼畸形,包括松弛多余的皮肤,arachnodactyly,平底,和关节挛缩。超声心动图显示心脏收缩力差,伴有多个瓣膜异常。她出生后13小时死亡。我们确定了一个新的错义变体c.3218A>G(p。通过靶向下一代测序,FBN1基因外显子26中的Glu1073Gly)。文献综述显示,胎儿的蛛网膜和主动脉根扩张可预测eoMFS。然而,仅超声检查的预测潜力是有限的.与短预期寿命和特征性胎儿超声检查结果相关的FBN1基因限制性区域的基因检测对于eoMFS的产前诊断可能很重要。产后管理,父母的准备。
■我们在一名出生后不久死于严重早期心力衰竭的早发性马凡综合征(eoMFS)新生儿中发现了一种位于Fibrillin-1基因外显子25-26的新错义突变。该突变位于狭窄的关键新生儿区域,最近报道导致eoMFS,其临床特征与早发性严重心力衰竭一致。除了超声检查,该区域的遗传分析对于预测eoMFS的预后很重要。
Early-onset Marfan syndrome (eoMFS) progresses rapidly, starting during the neonatal period, causes severe clinical disease, and has a poor prognosis. The genetic abnormality associated with eoMFS is located in a so-called critical neonatal region in exons 25-26 of the fibrillin-1 (FBN1) gene. A female neonate was delivered by emergency cesarean section at 37 weeks gestation due to fetal distress with bradycardia, cyanosis, and no spontaneous breathing. On examination, the patient had multiple musculoskeletal deformities, including loose redundant skin,
arachnodactyly, flat soles, and joint contractures. Echocardiography showed poor cardiac contractility with multiple valvular abnormalities. She died 13 h after birth. We identified a novel missense variant c.3218A>G (p.Glu1073Gly) in exon 26 of the FBN1 gene by targeted next-generation sequencing. A literature review revealed that
arachnodactyly and aortic root dilatation in the fetus are predictive of eoMFS. However, the predictive potential of ultrasonography alone is limited. Genetic testing of the FBN1 gene restriction region associated with short life expectancy and characteristic fetal ultrasound findings could be important for prenatal diagnosis of eoMFS, postnatal management, and parental preparedness.
UNASSIGNED: We identified a novel missense mutation located in exons 25-26 of the Fibrillin-1 gene in a neonate with early-onset Marfan syndrome (eoMFS) who died of severe early heart failure shortly after birth. This mutation was located in a narrowly defined critical neonatal region, recently reported to cause eoMFS, and its clinical profile was consistent with early-onset severe heart failure. In addition to ultrasonography, genetic analysis of this region is important for predicting prognosis in eoMFS.