A novel large in-frame FBN1 deletion causes neonatal Marfan syndrome

Cold Spring Harb Mol Case Stud. 2022 Oct 28;8(6):a006213. doi: 10.1101/mcs.a006213. Print 2022 Oct.


Neonatal Marfan syndrome (nMFS) is a rare and severe form of Marfan syndrome (MFS) with a poor prognosis, that presents with a highly variable phenotype, particularly regarding skeletal, ocular, and cardiovascular manifestations. Mutations in the fibrillin-1 (FBN1) gene are known as the principal cause of MFS and MFS-related syndromes. Here, we report on a full-term female neonate with postnatal characteristics suggestive of nMFS, including severe cardiovascular disease resulting in cardiorespiratory failure and death by 4 mo of age. We identified a novel large genomic in-frame deletion of FBN1 exons 42-45, c.(5065 + 1_5066 - 1)_(5545 + 1_5546 - 1)del. Large FBN1 in-frame deletions between exons 24 and 53 have been associated with severe MFS. The deletion in our patient differs from the FBN1 region associated with the majority of nMFS cases, exons 24-32.

Keywords: aortic aneurysm; arachnodactyly; cardiomegaly; hyperextensible thumb; microretrognathia; pulmonary hypertension; pulmonary valve defects; tricuspid regurgitation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons / genetics
  • Female
  • Fibrillin-1 / genetics
  • Humans
  • Marfan Syndrome* / genetics
  • Mutation
  • Phenotype
  • Sequence Deletion / genetics


  • FBN1 protein, human
  • Fibrillin-1