[en] Early-onset Marfan syndrome (eoMFS) is a severe and rare form of Marfan syndrome characterized by severe atrioventricular valve insufficiency developing before or shortly after birth. It is unclear which factors (interventions and/or genotype) influence survival. Forty-one individuals with eoMFS with a fibrillin-1 gene (FBN1) variant in exon 24-32 (CRCh37) were included. At the last follow-up, 14/41 (34%) were alive (8 months-18 years) and 27/41 (66%) were deceased. Median age of death was 1 month and 88% of the deaths occurred before 5 months of age. More individuals alive past the age of 16 months versus those who were deceased before that age had undergone cardiovascular surgery at an older age (13 months, range 3-72, vs. 2 months, range 2-2, p = 0.03). Survival was better in those with single amino acid substitutions/small in-frame deletions than in those with large in-frame deletions (p = 0.007), but variants involving a cysteine substitution in an EGF-like domain versus those involving other amino acids did not significantly influence survival. EoMFS ranges from a (pre-)neonatal life-threatening disorder to a disorder with enhanced survival, creating a window for cardiovascular surgery. Individuals with single amino acid substitutions/small in-frame deletions had better survival compared to those with variants significantly impacting exon 24-32 length.
Disciplines :
Pediatrics Cardiovascular & respiratory systems
Author, co-author :
van der Leest, Eva C; Department of Pediatrics, Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands ; Amsterdam Reproduction & Development, Amsterdam, the Netherlands
van der Hulst, Annelies E; Department of Pediatric Cardiology, Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands
Pals, Gerard; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Zhytnik, Lidiia; Amsterdam Reproduction & Development, Amsterdam, the Netherlands ; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands ; Rare Bone Disease Center Amsterdam, Amsterdam, the Netherlands ; Amsterdam Movement Sciences, Rehabilitation and Development, Amsterdam, the Netherlands ; Department of Endocrinology and Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands ; Department of Traumatology and Orthopaedics, The University of Tartu, Tartu, Estonia
Lai, Lillian; Division of Cardiology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
Jacquemart, Caroline ; Université de Liège - ULiège > Département des sciences cliniques
Mills, Lindsay; Division of Cardiology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
Houben, Michiel; Department of Pediatrics, University Medical Center, Wilhelmina Kinderziekenhuis, Utrecht, the Netherlands
Jira, Petr; Department of Pediatrics, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, the Netherlands
Lunshof, Bert L; Department of Pediatrics, Gelre Ziekenhuizen, Apeldoorn, the Netherlands
Warnink-Kavelaars, Jessica ; Amsterdam Movement Sciences, Rehabilitation and Development, Amsterdam, the Netherlands ; Department of Rehabilitation Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
de Waard, Vivian; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands ; Amsterdam Cardiovascular Sciences, Atherosclerosis and Ischemic Syndromes, Amsterdam, the Netherlands
Menke, Leonie A; Department of Pediatrics, Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands ; Amsterdam Reproduction & Development, Amsterdam, the Netherlands ; Amsterdam Neuroscience-Cellular & Molecular Mechanisms, Amsterdam, the Netherlands ; Emma Center for Personalized Medicine, Amsterdam, the Netherlands
This study was supported with a grant from Emma Children's Hospital Foundation (WAR2020\u201020). LAM was financially supported by funds of the academic education and research sector plans of the Dutch Ministry of Education, Culture and Science. We thank Dimitra Micha and Alessandra Maugeri for reviewing the interpretation of the variant classification. FBN1
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