Abstract
Purpose
This study aimed to develop objective diagnostic criteria for early onset Marfan syndrome
(eoMFS) to facilitate early diagnosis and timely interventions.
Methods
On the basis of an extensive literature review and the responses from a survey distributed
among providers with expertise in the diagnosis and management of eoMFS, we developed
an age-based, diagnostic scoring system encompassing 10 features common to eoMFS (9
clinical + 1 laboratory) and divided them into cardiac, systemic, and FBN1 (on the
basis of the location of the pathogenic FBN1 variant) scores.
Results
In total, 77 individuals with eoMFS (13 newly reported) and 49 individuals diagnosed
with classical Marfan syndrome during early childhood were used to validate the criteria.
Median cardiac (8 vs 0, P < .001), systemic (11 vs 3, P < .001), FBN1 (5 vs 0, P < .001), and total (23 vs 4, P < .001) scores were significantly higher in individuals with eoMFS than in those
without. A proposed clinical score (cardiac + systemic) cutoff of ≥14 points showed
excellent sensitivity (100%), specificity (92%), and reliability (correctly classified =
94%).
Conclusion
Distinct from classical Marfan syndrome in phenotype and morbidity, eoMFS can be diagnosed
clinically using an objective scoring system encompassing the typical physical features
and cardiac disease manifestations. Although genetic testing can be suggestive of
eoMFS, genetic testing alone is insufficient for diagnosis.
Keywords
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References
- FBN1-related Marfan syndrome.in: Adam M.P. Ardinger H.H. Pagon R.A. GeneReviews®. University of Washington, 1993
- Diagnosis and management of infantile Marfan syndrome.Pediatrics. 1990; 86: 888-895
- Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies.Hum Mutat. 2002; 20: 153-161https://doi.org/10.1002/humu.10113
- 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
- Severe infantile Marfan syndrome versus neonatal Marfan syndrome.Am J Med Genet A. 2005; 139: 1https://doi.org/10.1002/ajmg.a.30979
- 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
- Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene.Am J Med Genet. 1996; 62: 233-242https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<233::AID-AJMG7>3.0.CO;2-U
- Prognosis factors in probands with an FBN1 mutation diagnosed before the age of 1 year.Pediatr Res. 2011; 69: 265-270https://doi.org/10.1203/PDR.0b013e3182097219
- Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study.Am J Hum Genet. 2007; 81: 454-466https://doi.org/10.1086/520125
- Early-onset Marfan syndrome: a case series.J Pediatr Genet. 2019; 8: 86-90https://doi.org/10.1055/s-0038-1675338
- Neonatal Marfan syndrome: a successful early multidisciplinary approach.BMJ Case Rep. 2014; 2014bcr2013202438https://doi.org/10.1136/bcr-2013-202438
- Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097https://doi.org/10.1371/journal.pmed.1000097
- Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome.Am J Cardiol. 1990; 65: 1230-1237https://doi.org/10.1016/0002-9149(90)90979-b
- The Marfan syndrome in early childhood: analysis of 15 patients diagnosed at less than 4 years of age.Am J Cardiol. 1983; 52: 353-358https://doi.org/10.1016/0002-9149(83)90138-8
- Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations.Pediatrics. 2009; 123: 391-398https://doi.org/10.1542/peds.2008-0703
- Neonatal Marfan syndrome.Am J Perinatol. 2019; 36: S74-S76https://doi.org/10.1055/s-0039-1691770
- A case of neonatal Marfan syndrome: a management conundrum and the role of a multidisciplinary team.Case Rep Pediatr. 2017; 20178952428https://doi.org/10.1155/2017/8952428
- Surgical management of mitral regurgitation in patients with Marfan syndrome during infancy and early childhood.Korean J Thorac Cardiovasc Surg. 2015; 48: 7-12https://doi.org/10.5090/kjtcs.2015.48.1.7
- Palliative mitral valve repair during infancy for neonatal Marfan syndrome.Ann Thorac Surg. 2016; 101: 1987-1988https://doi.org/10.1016/j.athoracsur.2015.06.115
- Neonatal Marfan syndrome: clinical report and review of the literature.Clin Dysmorphol. 2005; 14: 81-84
- Mitral valve replacement in infants and children 5 years of age or younger: evolution in practice and outcome over three decades with a focus on supra-annular prosthesis implantation.J Thorac Cardiovasc Surg. 2008; 136: 954-961.e1-3https://doi.org/10.1016/j.jtcvs.2007.12.076
- Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome.Pediatr Neonatol. 2018; 59: 211-213https://doi.org/10.1016/j.pedneo.2017.07.005
- Impact of age and gender on cardiac pathology in children and adolescents with Marfan syndrome.Pediatr Cardiol. 2013; 34: 991-998https://doi.org/10.1007/s00246-012-0593-0
- Doxycycline delays aneurysm rupture in a mouse model of Marfan syndrome.J Vasc Surg. 2008; 47 (discussion 172.): 166-172https://doi.org/10.1016/j.jvs.2007.09.016
- Atenolol versus losartan in children and young adults with Marfan’s syndrome.N Engl J Med. 2014; 371: 2061-2071https://doi.org/10.1056/NEJMoa1404731
- NGS analysis in Marfan syndrome spectrum: combination of rare and common genetic variants to improve genotype-phenotype correlation analysis.PLoS One. 2019; 14e0222506https://doi.org/10.1371/journal.pone.0222506
- Identification of 29 novel and nine recurrent fibrillin-1 (FBN1) mutations and genotype-phenotype correlations in 76 patients with Marfan syndrome.Hum Mutat. 2005; 26: 529-539https://doi.org/10.1002/humu.20239
- Genotype-phenotype correlation in children: the impact of FBN1 variants on pediatric Marfan care.Genes (Basel). 2020; 11: 799https://doi.org/10.3390/genes11070799
- Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.Am J Hum Genet. 1995; 57: 8-21
Article info
Publication history
Published online: April 14, 2022
Accepted:
March 17,
2022
Received in revised form:
March 16,
2022
Received:
December 15,
2021
Identification
Copyright
© 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
