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.
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Cardiology Cases
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Marfan’s syndrome.Lancet. 2005; 366: 1965-1976https://doi.org/10.1016/S0140-6736(05)67789-6
- The molecular genetics of marfan syndrome and related disorders.J Med Genet. 2006; 43: 769-787https://doi.org/10.1136/jmg.2005.039669
- Novel exon skipping mutation in the fibrillin-1 gene: two “hot spots” for the neonatal marfan syndrome.Clin Genet. 1999; 55: 110-117https://doi.org/10.1034/J.1399-0004.1999.550207.X
- Classic, atypically severe and neonatal marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24–40.Eur J Hum Genet. 2001; 9: 13-21https://doi.org/10.1038/sj.ejhg.5200582
- A novel fibrillin-1 gene missense mutation associated with neonatal marfan syndrome: a case report and review of the mutation spectrum.BMC Pediatr. 2016; 16: 60https://doi.org/10.1186/S12887-016-0598-6
- Early-onset Marfan syndrome: a case series.J Pediatr Genet. 2019; 8: 86-90https://doi.org/10.1055/S-0038-1675338
- Prenatal diagnosis of marfan syndrome by fetal echocardiography: a case report and review of cardiovascular manifestations.Echocardiography. 2020; 37: 359-362https://doi.org/10.1111/echo.14577
- Perinatal diagnosis and management of early-onset marfan syndrome: case report and systematic review.J Matern Fetal Neonatal Med. 2020; 33: 2493-2504https://doi.org/10.1080/14767058.2018.1552935
- Narrowing of the neonatal region in the FBN1 gene.Eur Heart J. 2021; 42ehab724.1998https://doi.org/10.1093/eurheartj/ehab724.1988
- MYH7 mutation identified by next-generation sequencing in three infant siblings with bi-ventricular noncompaction presenting with restrictive hemodynamics: a report of three siblings with a severe phenotype and poor prognosis.J Cardiol Cases. 2019; 19: 140-143https://doi.org/10.1016/j.jccase.2018.12.017
Published online: March 10, 2023
Accepted: February 9, 2023
Received in revised form: January 28, 2023
Received: September 28, 2022
Publication stageIn Press Corrected Proof
© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.