TY - CHAP M1 - Book, Section TI - Achondroplasia A1 - Webb, Bryn D. A1 - Hoover-Fong, Julie E. A1 - Wang Jabs, Ethylin A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. Y1 - 2014 N1 - T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Achondroplasia is the most common form of inherited short stature.Incidence is approximately 1 in 15,000 to 1 in 40,000 live births.Clinical features include rhizomelic disproportionate short stature, macrocephaly, midface hypoplasia, trident hand conformation with brachydactyly, lordosis, genu varum, and normal cognitive development.Neurologic complications occur with cervicomedullary cord compression, spinal stenosis, and kyphosis. Potential respiratory complications include central sleep apnea due to cervicomedullary cord compression, and mechanical sleep apnea due to midface hypoplasia and relatively large adenotonsillar tissue compounded by hypotonia.Hereditary basis:Achondroplasia is inherited in an autosomal dominant fashion and has 100% penetrance.Approximately 99% of patients with achondroplasia have a point mutation (G changed to an A or G changed to a C) at nucleotide 1138 in the gene fibroblast growth factor receptor 3 (FGFR3) located at chromosome 4p16.3. This nucleotide change (G>A or G>C) results in a Gly380Arg amino acid substitution.Approximately 80% of patients with achondroplasia are born to parents of average height without FGFR3 mutations. De novo mutations have been associated with advanced paternal age.Differential diagnosis:Achondroplasia can be distinguished from other forms of disproportionate short stature including hypochondroplasia (OMIM 146000) and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), both caused by different FGFR3 mutations. Thanatophoric dysplasia I (OMIM 187600) and thanatophoric dysplasia II (OMIM 187601) are also caused by mutations in FGFR3, but are easily differentiated from achondroplasia by their more severe pulmonary phenotype and lethality. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessmedicine.mhmedical.com/content.aspx?aid=1102706553 ER -