Achondroplasia
From bonepath
Achondroplasia is a congenital condition resulting in dwarfism. The abnormality has been traced to a mutation of the FGFR3 gene on chromosome 4 (Shiang et al. 2004). As the condition follows autosomal-dominant inheritance, so possessing one allele with the mutation will result in achondroplasia; the majority of cases, however, arise from novel mutations in the parental (viz. paternal) germline; that is, neither of the parents usually has the condition passed on to the offspring (Sillence et al. 1979, Wynn et al. 2007). It is estimated that achondroplastic dwarfism occurs in about 1 of 25,000 live births (Oberklaid et al. 1979; Aufderheide and Rodriguez-Martin [1998] give the figure 1/10,000 but do not provide a reference). Although many conditions can cause dwarfism, achondroplasia is the most common.
The FGFR3 mutation of achondroplasia results in a failure of endochondral bone to form. Thus, dwarfism is caused by the failure of long bones to increase by apposition at epiphyses. Most often this manifests in especially foreshortened proximal limb segments (“rhizomelia”) with “stubby hands” (Waldron 2009: 200), as well as short vertebrae and an extremely lordotic (flexed) lumbar spine. The cranial base which grows through endochondral (rather than intramembranous) ossification is affected similar to the axial skeleton (viz. occipital bone: Keith 1913). Associated cranial morphology includes: a small foramen magnum, a short and narrow cranial base which is often highly flexed, poorly-pneumatized mastoids, a depressed nasal bridge, a bulging forehead, short (ethmoid) cribriform plate, and petrous temporal hypoplasia (Keith 1913, Langer et al. 1967, Sillence et al. 1979, Dixon et al. 1997, Aufderheide and Rodgriguez-Martin, Waldron 2009).
While the shape of the cranial vault is affected by achondroplasia, the brain is otherwise ‘normal’ and not usually associated with mental disability (Aufderheide and Rodriguez-Martin 1998). As mentioned above, most cases of achondroplasia are heterozygous (usually a paternally-derived mutation: Wynn et al. 2007) and individuals live a long time (Sillence et al. 1979). However, homozygous cases (i.e. both parents were achondroplastic dwarfs) often experience respiratory failure and die in only a few years (ibid). Wynn and colleagues (2007) found that there is an increased mortality risk, and 10-times increased prevalence of heart disease-related mortality, among achondroplastic adults (in Texas) than in the general population. These researchers also noted than many achondroplastic individuals also experience pain and mobility complications due to lumbosacral spinal stenosis (narrowing).
[edit] Examples from Ford Collection
[edit] References
Aufderheide AC, Rodriguez-Martin C, Langsjoen O. 1998. The Cambridge Encyclopedia of Human Paleopathology. Cambridge Univ Press
Dixon AD, Hoyte DAN, Rönning O. 1997. Fundamentals of craniofacial growth. CRC Press
Keith A. 1913. Abnormal Crania-Achondroplastic and Acrocephalic. J Anat Physiol 47:189-206
Langer LO, Baumann PA, Gorlin RJ. 1967. Achondroplasia. Am J Roentgenol 100:12-26
Oberklaid F, Danks DM, Jensen F, Stace L, Rosshandler S. 1979. Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine. Journal of medical genetics 16:140
Shiang R, Thompson LM, Zhu YZ, Church DM, et al. 1994. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78:335-42
Sillence DO, Horton WA, Rimoin DL. 1979. Morphologic studies in the skeletal dysplasias. The American Journal of Pathology 96:813
Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT. 2007. Mortality in achondroplasia study: A 42-year follow-up. Am J Med Genet A 143A:2502-11
