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.