Discussion
eoMFS is a rare and severe subtype of MFS. The eoMFS phenotype may be expressed in antenatal, neonatal, or infancy periods. However, the definition of eoMFS is controversial. Some authors suggest it to be the most serious subtype diagnosed in the perinatal period (1), while others suggest naming this form of MFS as infant MFS (2). Furthermore, most authors do not distinguish between eoMFS and neonatal MFS (nMFS). Hennekam (3) proposed that nMFS should be strictly applied to neonatal patients with severe mitral and/or tricuspid insufficiency and congenital pulmonary emphysema to indicate that it is a specific and severe form of MFS. In summary, eoMFS is more broadly defined than nMFS. The case presented here is more appropriately defined as eoMFS.
eoMFS is not easily diagnosed prenatally, even when ultrasound findings are present, because these are usually ambiguous and of late presentation. A systematic review by Veiga-Fernandez et al. of 39 articles gathering data from 54 cases, showed 34.54% of cases had prenatal ultrasound anomalies that helped raise the prenatal suspicion of eoMFS, while 65.45% were diagnosed in the postnatal period, without prenatal ultrasound findings (4). The most common prenatal findings were atrioventricular valvular prolapse and regurgitation. The next most common finding was cardiomegaly, followed by dilation of the great vessels. Among the cases with postnatal diagnosis, the most frequent cardiac ultrasound findings were pulmonary and aortic dilatation. The next most common findings were atrioventricular valvular prolapse and regurgitation. Cardiomegaly was the final cardiac manifestation. In our case, cardiac involvement of this patient appeared early and progressed rapidly. The main manifestations were aortic sinus dilation and atrioventricular valvular prolapse, which are consistent with the reported characteristics of eoMFS.
MFS is generally an autosomal dominant disorder with variable expressivity caused by mutations in FBN1 . Approximately 75% of classic MFS cases are hereditary, while eoMFS is mainly sporadic (5). Varied changes in protein domains caused by these point mutations lead to diverse clinical phenotypes. Mutations in exons 24 to 32 are closely related to nMFS or eoMFS (6). Exons 24 to 32 are located in the center of the cbEGF domain and play an important role in the distribution and stability of microfibers (7). In our case, the FBN1 mutation was located in exon 25. The mutation caused the glycine at position 1013 to be replaced by valine, which has a devastating effect on the formation of microfibrils.
Cardiovascular involvement appears early in children with eoMFS and their prognosis is poor. Echocardiography is of great significance for the diagnosis of eoMFS. For children with dilated aortic sinuses and atrioventricular regurgitation, the possibility of eoMFS should be considered. Early diagnosis, close follow-up, and timely treatment have a positive effect on improving the prognosis and quality of life of patients.