TY - JOUR
T1 - Marfan syndrome resulting from a rare pathogenic FBN1 variant, ascertained through a proband with IgG4-related arteriopathy
AU - Haan, Eric A.
AU - Chamalaun, Francois H.
AU - Chamuleau, S.A.J.
AU - Arnolda, Leonard F.
AU - Slavotinek, John P.
AU - Wise, Nadia C.
AU - Gunawardane, Dimuth N.
AU - Schwarze, Ulrike
AU - Byers, Peter H.
AU - Gabb, Genevieve M.
N1 - Funding Information: We thank the proband's family for participation and access to their clinical information and genetic test results, Dr Andrew Russell for reviewing the proband's echocardiograms, Dr Fahmida Ilyas for reviewing the proband's MRI images and Dr Anne Nguyen-Hoang for assisting with review of original 1995 aortic histopathology. Publisher Copyright: © 2021 Wiley Periodicals LLC. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - A 57-year-old man with a family history of aortic aneurysm was found, during assessment of unexplained fever, to have an infrarenal aortic aneurysm requiring immediate repair. Dilatation of popliteal and iliac arteries was also present. Progressive aortic root dilatation with aortic regurgitation was documented from 70 years leading to valve-sparing aortic root replacement at 77 years, at which time genetic studies identified a likely pathogenic FBN1 missense variant c.6916C > T (p.Arg2306Cys) in exon 56. The proband's lenses were normally positioned and the Marfan syndrome (MFS) systemic score was 0/20. Cascade genetic testing identified 15 other family members with the FBN1 variant, several of whom had unsuspected aortic root dilatation; none had ectopia lentis or MFS systemic score ≥ 7. Segregation analysis resulted in reclassification of the FBN1 variant as pathogenic. The combination of thoracic aortic aneurysm and dissection (TAAD) and a pathogenic FBN1 variant in multiple family members allowed a diagnosis of MFS using the revised Ghent criteria. At 82 years, the proband's presenting abdominal aortic aneurysm was diagnosed retrospectively to have resulted from IgG4-related inflammatory aortopathy.
AB - A 57-year-old man with a family history of aortic aneurysm was found, during assessment of unexplained fever, to have an infrarenal aortic aneurysm requiring immediate repair. Dilatation of popliteal and iliac arteries was also present. Progressive aortic root dilatation with aortic regurgitation was documented from 70 years leading to valve-sparing aortic root replacement at 77 years, at which time genetic studies identified a likely pathogenic FBN1 missense variant c.6916C > T (p.Arg2306Cys) in exon 56. The proband's lenses were normally positioned and the Marfan syndrome (MFS) systemic score was 0/20. Cascade genetic testing identified 15 other family members with the FBN1 variant, several of whom had unsuspected aortic root dilatation; none had ectopia lentis or MFS systemic score ≥ 7. Segregation analysis resulted in reclassification of the FBN1 variant as pathogenic. The combination of thoracic aortic aneurysm and dissection (TAAD) and a pathogenic FBN1 variant in multiple family members allowed a diagnosis of MFS using the revised Ghent criteria. At 82 years, the proband's presenting abdominal aortic aneurysm was diagnosed retrospectively to have resulted from IgG4-related inflammatory aortopathy.
KW - FBN1
KW - IgG4-related disease
KW - Marfan syndrome
KW - arterial aneurysm
KW - familial thoracic aortic aneurysm
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85104505325&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33878224
UR - http://www.scopus.com/inward/record.url?scp=85104505325&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajmg.a.62218
DO - https://doi.org/10.1002/ajmg.a.62218
M3 - Article
C2 - 33878224
SN - 1552-4825
VL - 185
SP - 2180
EP - 2189
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 7
ER -