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Achrondoplasia

Achondroplasia

Genetic condition, the most common form of dwarfism

Medical condition

Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism.^[3] It is the most common cause of dwarfism^[4] and affects about 1 in 27,500 people.^[3] In those with the condition, the arms and legs are short, while the torso is typically of normal length.^[3] Those affected have an average adult height of 131 centimetres (4 ft 4 in) for males and 123 centimetres (4 ft) for females.^[3] Other features can include an enlarged head with prominent forehead (frontal bossing)^[3] and underdevelopment of the midface (midface hypoplasia).^[6] Complications can include sleep apnea or recurrent ear infections.^[3] Achondroplasia includes the extremely rare short-limb skeletal dysplasia with severe combined immunodeficiency.

Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that results in its protein being overactive.^[3] Achondroplasia results in impaired endochondral bone growth (bone growth within cartilage).^[7] The disorder has an autosomal dominant mode of inheritance, meaning only one mutated copy of the gene is required for the condition to occur.^[8] About 80% of cases occur in children of parents without the disease, and result from a new (de novo, or sporadic) mutation, which most commonly originates as a spontaneous change during spermatogenesis.^[5] The rest are inherited from a parent with the condition.^[3] The risk of a new mutation increases with the age of the father.^[4] In families with two affected parents, children who inherit both affected genes typically die before birth or in early infancy from breathing difficulties.^[3] The condition is generally diagnosed based on the clinical features but may be confirmed by genetic testing.^[5] Mutations in FGFR3 also cause achondroplasia related conditions including hypochondroplasia and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities resulting in severe short-limb skeletal dysplasia with severe combined immunodeficiency.^[9]

Treatments include small molecule therapy with a C-natriuretic peptide analog (vosoritide), approved to improve growth velocity in children with achondroplasia based on results in Phase 3 human trials, although its long-term effects are unknown.^[10] Growth hormone therapy may also be used.^[5] Efforts to treat or prevent complications such as obesity, hydrocephalus, obstructive sleep apnea, middle ear infections or spinal stenosis may be required.^[5] Support groups support people with achondroplasia, including the Little People of America (LPA) and Growing Stronger. Nonprofit physician organizations also exist to disseminate information about treatment and management options, including development of patient resources.

1. ^ "Achondroplasia". Lexico UK English Dictionary. Oxford University Press. Archived from the original on 11 December 2019.
2. ^ "Achondroplasia". Merriam-Webster.com Dictionary.
3. ^ ^{a b c d e f g h i j k l m n} "Achondroplasia". Genetics Home Reference. May 2012. Retrieved 12 December 2017.
4. ^ ^{a b c} Cite error: The named reference Lancet2007 was invoked but never defined (see the help page).
5. ^ ^{a b c d e f g} Pauli RM, Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Mefford HC, Stephens K, Amemiya A, Ledbetter N (2012). "Achondroplasia". GeneReviews. PMID 20301331.
6. ^ White KK, Bompadre V, Goldberg MJ, Bober MB, Campbell JW, Cho TJ, Hoover-Fong J, Mackenzie W, Parnell SE, Raggio C, Rapoport DM, Spencer SA, Savarirayan R (1 January 2016). "Best practices in the evaluation and treatment of foramen magnum stenosis in achondroplasia during infancy". American Journal of Medical Genetics Part A. 170 (1): 42–51. doi:10.1002/ajmg.a.37394. ISSN 1552-4825. PMID 26394886. S2CID 22430204.
7. ^ Pauli RM (2019). "Achondroplasia: A comprehensive clinical review". Orphanet Journal of Rare Diseases. 14 (1): 1. doi:10.1186/s13023-018-0972-6. PMC 6318916. PMID 30606190.
8. ^ "Achondroplasia". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2016. Retrieved 12 December 2017.
9. ^ Legare JM (1993), Adam MP, Feldman J, Mirzaa GM, Pagon RA (eds.), "Achondroplasia", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID 20301331, retrieved 15 December 2023
10. ^ Cite error: The named reference :0 was invoked but never defined (see the help page).

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