A clinical scoring system for early onset (neonatal) Marfan syndrome

Yuri A. Zarate; Shaine A. Morris; Anna Blackshare; Claudia A. Algaze; Brynn S. Connor; Andrew J. Kim; Katherine E. Yutzey; Erin M. Miller; Kathryn Nicole Weaver; Ronnie Thomas Collins

doi:10.1016/j.gim.2022.03.016

A clinical scoring system for early onset (neonatal) Marfan syndrome

Yuri A. Zarate
, Shaine A. Morris
, Anna Blackshare
, Claudia A. Algaze
, Brynn S. Connor
, Andrew J. Kim
, Katherine E. Yutzey
, Erin M. Miller
, Kathryn Nicole Weaver
, Ronnie Thomas Collins

Pediatrics

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Pages (from-to)	1503-1511
Number of pages	9
Journal	Genetics in Medicine
Volume	24
Issue number	7
DOIs	https://doi.org/10.1016/j.gim.2022.03.016
State	Published - Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 American College of Medical Genetics and Genomics

Funding

The authors would like to thank the providers who responded to the initial survey. Support for REDCap was made possible through the University of Arkansas for Medical Sciences Translational Research Institute (NCATS/NIH UL1 RR029884). Conceptualization: Y.A.Z. S.A.M. A.B. R.T.C.; Formal Analysis: Y.A.Z. A.B. C.A.A. B.S.C.; Investigation: Y.A.Z. S.A.M. A.B. A.J.K. K.E.Y. E.M.M. K.N.W. R.T.C.; Resources: Y.A.Z. C.A.A. B.S.C.; Writing-original draft: Y.A.Z. R.T.C.; Writing-review and editing: Y.A.Z. S.A.M. C.A.A. K.E.Y. E.M.M. K.N.W. R.T.C. Approval for the review and reporting of these cases was given by the Institutional Review Board of the University of Arkansas for Medical Sciences. Data from the survey distributed to the providers were anonymized. Written informed consent was obtained from individual ID#62 for the scientific use of photo documentation.

Funders	Funder number
National Institutes of Health (NIH)	UL1 RR029884
National Center for Advancing Translational Sciences (NCATS)
University of Arkansas for Medical Sciences
Translational Research Institute, University of Arkansas for Medical Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

FBN1
Marfan syndrome
Neonate
Severe cardiovascular disease
Severe early onset

ASJC Scopus subject areas

Genetics(clinical)

Access to Document

10.1016/j.gim.2022.03.016

Cite this

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title = "A clinical scoring system for early onset (neonatal) Marfan syndrome",

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 = "FBN1, Marfan syndrome, Neonate, Severe cardiovascular disease, Severe early onset",

author = "Zarate, \{Yuri A.\} and Morris, \{Shaine A.\} and Anna Blackshare and Algaze, \{Claudia A.\} and Connor, \{Brynn S.\} and Kim, \{Andrew J.\} and Yutzey, \{Katherine E.\} and Miller, \{Erin M.\} and Weaver, \{Kathryn Nicole\} and Collins, \{Ronnie Thomas\}",

note = "Publisher Copyright: {\textcopyright} 2022 American College of Medical Genetics and Genomics",

year = "2022",

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doi = "10.1016/j.gim.2022.03.016",

language = "English",

volume = "24",

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AU - Zarate, Yuri A.

AU - Morris, Shaine A.

AU - Blackshare, Anna

AU - Algaze, Claudia A.

AU - Connor, Brynn S.

AU - Kim, Andrew J.

AU - Yutzey, Katherine E.

AU - Miller, Erin M.

AU - Weaver, Kathryn Nicole

AU - Collins, Ronnie Thomas

PY - 2022/7

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N2 - 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.

AB - 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.

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KW - Neonate

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A clinical scoring system for early onset (neonatal) Marfan syndrome

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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