Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype

J Bone Miner Res. 2015 Aug;30(8):1369-76. doi: 10.1002/jbmr.2471. Epub 2015 May 14.


Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutation in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1), leading to transforming growth factor-beta (TGF-β) signaling dysregulation. Although decreased axial and peripheral bone mineral density (BMD) has been reported in adults with MFS, data about the evolution of bone mass during childhood and adolescence are limited. The aim of the present study was to evaluate bone and muscle characteristics in children, adolescents, and young adults with MFS. The study population included 48 children and young adults (22 girls) with MFS with a median age of 11.9 years (range 5.3 to 25.2 years). The axial skeleton was analyzed at the lumbar spine using dual-energy X-ray absorptiometry (DXA), whereas the appendicular skeleton (hand) was evaluated using the BoneXpert system (with the calculation of the Bone Health Index). Muscle mass was measured by DXA. Compared with healthy age-matched controls, bone mass at the axial and appendicular levels and muscle mass were decreased in children with MFS and worsened from childhood to adulthood. Vitamin D deficiency (<50 nmol/L) was found in about a quarter of patients. Serum vitamin D levels were negatively correlated with age and positively correlated with lumbar spine areal and volumetric BMD. Lean body mass (LBM) Z-scores were positively associated with total body bone mineral content (TB-BMC) Z-scores, and LBM was an independent predictor of TB-BMC values, suggesting that muscle hypoplasia could explain at least in part the bone loss in MFS. Patients with a FBN1 premature termination codon mutation had a more severe musculoskeletal phenotype than patients with an inframe mutation, suggesting the involvement of TGF-β signaling dysregulation in the pathophysiologic mechanisms. In light of these results, we recommend that measurement of bone mineral status should be part of the longitudinal clinical investigation of MFS children.


Publication types

  • Clinical Trial

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aging* / genetics
  • Aging* / pathology
  • Bone Density
  • Child
  • Child, Preschool
  • Codon, Terminator
  • Cross-Sectional Studies
  • Female
  • Fibrillin-1
  • Fibrillins
  • Follow-Up Studies
  • Genotype*
  • Humans
  • Male
  • Marfan Syndrome* / diagnostic imaging
  • Marfan Syndrome* / genetics
  • Marfan Syndrome* / physiopathology
  • Microfilament Proteins / genetics*
  • Muscle, Skeletal* / diagnostic imaging
  • Muscle, Skeletal* / physiopathology
  • Spine* / diagnostic imaging
  • Spine* / physiopathology


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