title: Primordial dwarfism: an update.
abstract: OBJECTIVE
  To review the recent advances in the clinical and molecular characterization of primordial dwarfism, an extreme growth deficiency disorder that has its onset during embryonic development and persists throughout life.
  
  
  RESULTS
  The last decade has witnessed an unprecedented acceleration in the discovery of genes mutated in primordial dwarfism, from one gene to more than a dozen genes. These genetic discoveries have confirmed the notion that primordial dwarfism is caused by defects in basic cellular processes, most notably centriolar biology and DNA damage response. Fortunately, the increasing number of reported clinical primordial dwarfism subtypes has been accompanied by more accurate molecular classification.
  
  
  CONCLUSIONS
  Qualitative defects of centrioles with resulting abnormal mitosis dynamics, reduced proliferation, and increased apoptosis represent the predominant molecular pathogenic mechanism in primordial dwarfism. Impaired DNA damage response is another important mechanism, which we now know is not mutually exclusive to abnormal centrioles. Molecular characterization of primordial dwarfism is helping families by enabling more reproductive choices and may pave the way for the future development of therapeutics.
authors.affiliation: aDepartment of Genetics, King Faisal Specialist Hospital and Research Center bDepartment of Anatomy and Cell Biology, College of Medicine, Alfasial University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D049109:Cell Proliferation; D004392:Dwarfism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019066:Facies; D055106:Genome-Wide Association Study; D006801:Humans; D008831:Microcephaly / Q000453:epidemiology / Q000235:genetics; D009154:Mutation / Q000235:genetics; D017410:Practice Guidelines as Topic