Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome

Eur J Hum Genet. 2016 Dec;24(12):1746-1751. doi: 10.1038/ejhg.2016.84. Epub 2016 Jul 6.


Spondylocarpotarsal synostosis syndrome (SCT) is a rare Mendelian disorder (OMIM #272460) characterized by prenatal vertebral fusion, scoliosis, short stature and carpal and tarsal synostosis. SCT is typically known as an autosomal recessive disease caused by variants in the FLNB gene. The genetic basis of the rarer cases of vertical transmissions remains unknown. In two independent families with symptoms related to autosomal dominant SCT, we identified - by exome sequencing - two protein-altering variants in the embryonic myosin heavy chain 3 (MYH3) gene. As MYH3 variants are also associated with distal arthrogryposis (DA1, DA2A, DA2B) and autosomal dominant multiple pterygium syndromes (MPS), the present study expands the phenotypic spectrum of MYH3 variants to autosomal dominant SCT. Vertebral, carpal and tarsal fusions observed in both families further confirm that MYH3 plays a key role in skeletal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Adult
  • Child
  • Cytoskeletal Proteins / genetics*
  • Exome
  • Female
  • Humans
  • Lumbar Vertebrae / abnormalities*
  • Lumbar Vertebrae / pathology
  • Male
  • Musculoskeletal Diseases / genetics*
  • Musculoskeletal Diseases / pathology
  • Mutation*
  • Pedigree
  • Phenotype*
  • Scoliosis / congenital*
  • Scoliosis / genetics
  • Scoliosis / pathology
  • Synostosis / genetics*
  • Synostosis / pathology
  • Thoracic Vertebrae / abnormalities*
  • Thoracic Vertebrae / pathology


  • Cytoskeletal Proteins
  • MYH3 polypeptide, human

Supplementary concepts

  • Spondylocarpotarsal synostosis