Advances in Skeletal Dysplasia Genetics

Annu Rev Genomics Hum Genet. 2015:16:199-227. doi: 10.1146/annurev-genom-090314-045904. Epub 2015 Apr 22.


Skeletal dysplasias result from disruptions in normal skeletal growth and development and are a major contributor to severe short stature. They occur in approximately 1/5,000 births, and some are lethal. Since the most recent publication of the Nosology and Classification of Genetic Skeletal Disorders, genetic causes of 56 skeletal disorders have been uncovered. This remarkable rate of discovery is largely due to the expanded use of high-throughput genomic technologies. In this review, we discuss these recent discoveries and our understanding of the molecular mechanisms behind these skeletal dysplasia phenotypes. We also cover potential therapies, unusual genetic mechanisms, and novel skeletal syndromes both with and without known genetic causes. The acceleration of skeletal dysplasia genetics is truly spectacular, and these advances hold great promise for diagnostics, risk prediction, and therapeutic design.

Keywords: ciliopathy; epigenetics; growth insufficiency; imprinting; mosaicism; primordial dwarfism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Height / genetics
  • Bone Diseases, Developmental / genetics*
  • Disease Models, Animal
  • Dwarfism / genetics
  • Epigenesis, Genetic
  • High-Throughput Nucleotide Sequencing / methods
  • Histone Acetyltransferases / genetics
  • Humans
  • Mice
  • MicroRNAs
  • Mutation*
  • Osteochondrodysplasias / genetics
  • Proteus Syndrome / genetics


  • MicroRNAs
  • Histone Acetyltransferases