Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene

Eur J Med Genet. 2014 Apr;57(5):230-4. doi: 10.1016/j.ejmg.2014.02.012. Epub 2014 Mar 6.


We report a 16-year-old girl with neonatal progeroid features and congenital lipodystrophy who was considered at birth as a possible variant of Wiedemann-Rautenstrauch syndrome. The emergence of additional clinical signs (marfanoid habitus, severe myopia and dilatation of the aortic bulb) lead to consider the diagnosis of the progeroid variant of Marfan syndrome. A de novo donor splice-site mutation (c.8226+1G>A) was identified in FBN1. We show that this mutation leads to exon 64 skipping and to the production of a stable mRNA that should allow synthesis of a truncated profibrillin-1, in which the C-terminal furin cleavage site is altered. FBN1 mutations associated with a similar phenotype have only been reported in four other patients. We confirm the correlation between marfanoid phenotype with congenital lipodystrophy and neonatal progeroid features (marfanoid-progeroid-lipodystrophy syndrome) and frameshift mutations at the 3' end of FBN1. This syndrome should be considered in differential diagnosis of neonatal progeroid syndromes.

Keywords: Congenital lipodystrophy; Fibrillinopathy; Marfanoïd features; Neonatal progeria.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Base Sequence
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Female
  • Fetal Growth Retardation / diagnosis*
  • Fetal Growth Retardation / genetics
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Lipodystrophy / congenital
  • Lipodystrophy / diagnosis*
  • Lipodystrophy / genetics
  • Marfan Syndrome / diagnosis*
  • Marfan Syndrome / genetics
  • Microfilament Proteins / genetics*
  • Molecular Diagnostic Techniques
  • Molecular Sequence Data
  • Progeria / diagnosis*
  • Progeria / genetics


  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins

Supplementary concepts

  • Progeroid syndrome, neonatal