title: Achondroplasia.
abstract: Achondroplasia is the most common form of short limb dwarfism in human beings, affecting more than 250,000 individuals worldwide. More than 95% of patients have the same point mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) and more than 80% of these are new mutations. The mutation, which causes gain of FGFR3 function, affects many tissues, most strikingly the cartilaginous growth plate in the growing skeleton, leading to a variety of manifestations and complications. The biology of FGFR3 and the molecular and cellular consequences of the achondroplasia mutation are being elucidated, providing a more complete understanding of the disorder and a basis for future treatments targeted directly at relevant pathogenetic pathways. Furthermore, the natural history of the condition, which has been well delineated in childhood and adolescence, is being defined more fully in adults with achondroplasia; most of the serious complications can be modified favourably or prevented by anticipation and early treatment. Possible future treatments include chemical inhibition of receptor signalling, antibody blockade of receptor activation, and alteration of pathways that modulate the downstream propagation of FGFR3 signals.
authors.affiliation: Research Center, Shriners Hospital for Children and Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA. Electronic address: wah@shcc.org.
authors.forename: William A
authors.initials: WA
authors.lastname: Horton
authors.affiliation: Departments of Pediatrics and Medical Genetics, University of British Columbia and Department of Pediatrics, British Columbia Children's Hospital, Vancouver, BC, Canada.
authors.forename: Judith G
authors.initials: JG
authors.lastname: Hall
authors.affiliation: Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000130:Achondroplasia / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D001846:Bone Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000502:physiology
chemical_list: D019382:Human Growth Hormone; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3