Abstract
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.
Learning objective
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.
Keywords
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Article info
Publication history
Published online: March 10, 2023
Accepted:
February 9,
2023
Received in revised form:
January 28,
2023
Received:
September 28,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
