Synonyms
Dwarfism for achondroplasia group; Ach
Definition and Characteristics
For Ach group, autosomal dominant FGFR3 mutations with complete penetrance leading to dwarfism and other defects, some of which are neonatal lethal. FGFR2 mutations are associated with craniosynostosis and syndactyly. SHOX haploinsufficiency, including in Turner’s syndrome, is associated with short stature and other skeletal defects.
Prevalence
For Ach group, prevalence varies from 1/10,000 to 1/40,000, with 7/8 of mutations being sporadic. SHOX is mutated in 2% of children with short stature.
Genes
FGFR3 on chromosome 4p16.3, FGFR2 on chromosome 10q25.3–q26. SHOX is on chromosome Xpter-p22.32, in pseudoautosomal region 1 (so not inactivated with X inactivation).
Molecular and Systemic Pathophysiology
Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases with an extracellular ligand binding domain consisting of three Ig domains, a transmembrane domain, and a cytoplasmic kinase domain (Fig.
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References
Blaschke RJ, Rappold GA (2000) SHOX: growth, Leri-Weill and Turner syndromes. Trends Endocrinol Metab 11:227–230
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Hart KC, Robertson SC, Donoghue DJ (2001) Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation. Mol Biol Cell 12:931–942
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Ogata T, Matsuo N, Nishimura G (2001) SHOX haploinsufficiency and overdosage: impact of gonadal function status. J Med Genet 38:1–6
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© 2009 Springer-Verlag GmbH Berlin Heidelberg
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Mac, S., Donoghue, D. (2009). Achondrodoplasia. In: Lang, F. (eds) Encyclopedia of Molecular Mechanisms of Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-29676-8_15
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DOI: https://doi.org/10.1007/978-3-540-29676-8_15
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-67136-7
Online ISBN: 978-3-540-29676-8
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