Soma Kana, Kitagawa Yosuke, Toki Tsutomu, Miura Fumitake, Shimada Jun, Sato Tomohiko, Kudo Ko, Otani Katsuki, Takahashi Toru, Terui Kiminori
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
J Cardiol Cases. 2023 Mar 10;27(6):283-286. doi: 10.1016/j.jccase.2023.02.019. eCollection 2023 Jun.
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 () 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 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 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.
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.
早发型马凡综合征（eoMFS）进展迅速，始于新生儿期，会导致严重的临床疾病，且预后不良。与eoMFS相关的基因异常位于（）基因第25 - 26外显子的一个所谓关键新生儿区域。一名女性新生儿因胎儿窘迫伴心动过缓、发绀且无自主呼吸，于妊娠37周时紧急剖宫产娩出。检查发现，该患者有多处肌肉骨骼畸形，包括皮肤松弛多余、蜘蛛指、扁平足和关节挛缩。超声心动图显示心脏收缩功能差，伴有多处瓣膜异常。她出生后13小时死亡。我们通过靶向二代测序在该基因第26外显子中鉴定出一个新的错义变异c.3218A>G（p.Glu1073Gly）。文献综述显示，胎儿的蜘蛛指和主动脉根部扩张可预测eoMFS。然而，仅超声检查的预测潜力有限。对与预期寿命短相关的该基因限制区域进行基因检测以及特征性的胎儿超声检查结果，对于eoMFS的产前诊断、产后管理及家长准备可能具有重要意义。
我们在一名早发型马凡综合征（eoMFS）新生儿中鉴定出一个位于原纤维蛋白-1基因第25 - 26外显子的新错义突变，该新生儿出生后不久死于严重的早期心力衰竭。此突变位于一个狭义定义的关键新生儿区域，最近报道该区域可导致eoMFS，其临床特征与早发型严重心力衰竭一致。除超声检查外，该区域的基因分析对于预测eoMFS的预后很重要。
