Achondroplasia: Difference between revisions
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'''Achondroplasia''' is a type of [[autosomal]] [[Dominance (genetics)|dominant]] [[genetic disorder]] that is a common cause of |
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[[dwarfism]]. Achondroplastic dwarfs have [[short stature]], with an average adult height of 131 [[centimeter|cm]] (4 [[Foot (unit of measure)|feet]], 3.8 inches) for males and 123 cm (4 feet, 0.6 inches) for females. |
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The prevalence is approximately 1 in 25,000.<ref name="pmid17879967">{{cite journal |author=Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT |title=Mortality in achondroplasia study: A 42-year follow-up |journal=Am. J. Med. Genet. A |volume=143 |issue=21 |pages=2502–11 |year=2007 |pmid=17879967 |doi=10.1002/ajmg.a.31919}}</ref> |
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== Epidemiology == |
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Achondroplasia is one of several [[congenital disorder|congenital condition]]s with similar presentations, such as [[osteogenesis imperfecta]], multiple epiphyseal dysplasia tarda, [[achondrogenesis]], [[osteopetrosis]], and [[thanatophoric dysplasia]]. This makes estimates of prevalence difficult, with changing and subjective diagnostic criteria over time. One detailed and long-running study in the Netherlands found that the prevalence determined at birth was only 1.3 per 100,000 live births<ref name=OMIM>{{OMIM|100800|ACHONDROPLASIA; ACH}}</ref>. However, another study at the same time found a rate of 1 per 10,000<ref name=OMIM/>. |
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==Causes== |
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Achondroplasia is a result of an [[autosomal dominant]] [[mutation]] in the [[fibroblast]] [[growth factor]] [[receptor (biochemistry)|receptor]] gene 3 ({{Gene|FGFR3}}), which causes an abnormality of [[cartilage]] formation. [[FGFR3]] normally has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. |
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Animals with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal before, or shortly after birth. Only one copy of the gene needs to be present for the disorder to occur. Therefore, a person with achondroplasia has a 50% chance of passing on the gene to their offspring, meaning that there will be a 50% chance that each child will have achondroplasia. Since two copies (Homozygous) are fatal, if two people with achondroplasia have a child, there is a 25% chance of the child dying shortly after birth, a 50% chance the child will have achondroplasia, and a 25% chance the child will have a normal [[phenotype]]. However, in the majority of cases, people with achondroplasia are born to parents who don't have the condition. This is the result of a new [[mutation]].<ref name="pmid17950653">{{cite journal |author=Richette P, Bardin T, Stheneur C |title=Achondroplasia: From genotype to phenotype |journal=Joint Bone Spine |volume= 75|issue= | pages = 125|year=2007 |pmid=17950653 |doi=10.1016/j.jbspin.2007.06.007}}</ref> |
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New gene mutations are associated with increasing paternal age<ref name="pmid17706214">{{cite journal |author=Dakouane Giudicelli M, Serazin V, Le Sciellour CR, Albert M, Selva J, Giudicelli Y |title=Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies |journal=Fertil Steril |volume= 89|issue= |pages= 1651|year=2007 |pmid=17706214 |doi=10.1016/j.fertnstert.2007.04.037}}</ref> (over 35 years). Studies have demonstrated that new gene mutations are exclusively inherited from the father and occur during [[spermatogenesis]] (as opposed to resulting from a [[gonadal mosaicism]]). More than 99% of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor 3 ([[FGFR3]]). In about 98% of cases, a G to A point mutation at [[nucleotide]] 1138 of the FGFR3 gene causes a [[glycine]] to [[arginine]] substitution (Bellus et al 1995, Shiang et al 1994, Rousseau et al 1996). About 1% of cases are caused by a G to C point mutation at nucleotide 1138. |
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There are two other syndromes with a genetic basis similar to achondroplasia: [[hypochondroplasia]] and [[thanatophoric dysplasia]]. |
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==Diagnosis== |
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Achondroplasia can be detected before birth by the use of [[Prenatal diagnosis|prenatal]] [[ultrasound]]. A [[DNA test]] can be performed before birth to detect [[Zygosity#Homozygous|homozygosity]], where two copies of the mutant gene are inherited, a condition which is lethal and leads to [[stillbirths]]. Other indicators of achondroplasia include slow motor movement and low muscle tone ([[hypotonia]]). One result of low muscle tone is that walking doesn't occur until between 24 and 36 months. Because of short stature, [[obesity]] is often associated with the condition. Children often have middle ear infections ([[otitis media]]) because of abnormal drainage of the tube from the middle ear to the throat due to the abnormal skull structure. To help with the drainage many children have a surgical procedure to place tubes in their ears. Because of abnormal skull structure, overcrowding of the teeth occurs and malocclusion often results, which makes oral hygiene difficult. |
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===Radiologic findings=== |
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A skeletal survey is useful to confirm the diagnosis of achondroplasia. Skull demonstrate a large skull with a narrow [[foramen magnum]], and relatively small skull base. The vertebral bodies are short and flattened with relatively large intervertebral disk height, and there is congenitally narrowed [[spinal canal]]. The iliac wings are small and squared,<ref name="titleAchondroplasia Pelvis">{{cite web |url=http://www.stevensorenson.com/residents6/achondroplasia_pelvis.htm |title=Achondroplasia Pelvis |accessdate=2007-11-28 |format= |work=}}</ref> with a narrow sciatic notch and horizontal acetabular roof. The tubular bones are short and thick with [[metaphyseal]] cupping and flaring and irregular growth plates. [[Fibular]] overgrowth is present. The hand is broad with short [[metacarpals]] and [[phalanges]], and a trident configuration. The ribs are short with cupped anterior ends. If the [[radiographic]] features are not classic, a search for a different diagnosis should be entertained. Because of the extremely deformed bone structure, people with achondroplasia are often [[Hypermobility|double jointed]]. |
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The diagnosis can be made by fetal [[ultrasound]] by progressive discordance between the [[femur]] length and biparietal diameter by age. The trident hand configuration can be seen if the fingers are fully extended. |
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==Treatment== |
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At present, there is no treatment for achondroplasia. |
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Although used by those without achondroplasia to aid in growth, [[growth hormone]] does not help people with achondroplasia. However, if desired, the controversial surgery of [[limb-lengthening]] will lengthen the legs and arms of someone with achondroplasia, although in some cases when this surgery is undergone, some affected individuals may experience their limbs becoming "locked to their torso".<ref name="pmid17717461">{{cite journal |author=Kitoh H, Kitakoji T, Tsuchiya H, Katoh M, Ishiguro N |title=Distraction osteogenesis of the lower extremity in patients with achondroplasia/hypochondroplasia treated with transplantation of culture-expanded bone marrow cells and platelet-rich plasma |journal=J Pediatr Orthop |volume=27 |issue=6 |pages=629–34 |year=2007 |pmid=17717461 |doi=10.1097/BPO.0b013e318093f523 |doi_brokendate=2008-06-25}}</ref> |
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==Miscellanous== |
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Reported by the Fox News Channel, [[Jyoti Amge]], a 14-year-old girl from India, broke the world record for the shortest person on earth. Diagnosed with achondroplasia, she is 23 inches (58 cm) tall, and weighs 11 lbs (5 kg).<ref>[http://www.foxnews.com/story/0,2933,348248,00.html FOXNews.com - Tiny Teenager Stands Tall Despite Her Height of 23 Inches - Incredible Health<!-- Bot generated title -->]</ref> |
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The condition was present in the pre-Columbian New World (evidence from the skeletal remains), and in documentation by skeletons, wall paintings, figurines in the ancient Egypt from pre-Dynastic times (up to 30th Dynasty). The ancient Egyptian word for people affected by the condition was nemew. They held various offices and were regarded as highly intelligent. Several of them must have been persons of importance and wealth, being found in elaborate tombs. <ref>[Encyclopedia of Medical Anthropology: Health and Illness in the World's Cultures Topics by Carol R. Ember, Melvin Ember]</ref> |
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==References== |
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{{reflist}} |
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==External links== |
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*[http://www.achondroplasia.co.uk Achondroplasia UK] The Number one UK website with over 500 members. |
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*[http://genome.wellcome.ac.uk/doc_wtd020861.html Description of Achondroplasia] from the [[Wellcome Trust]] Human Genome site |
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*[http://www.kromosoft.com/resources/KB/Abstracts/GeneticsOfAchondroplasia.php Genetics of Achondroplasia] |
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*[http://uwmsk.org/moodle/mod/resource/view.php?id=408 Achondroplasia] by Kathleen Tozer, M.D. & Bart Keogh, M.D., University of Washington Department of Radiology |
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*[http://www.rad.washington.edu/mskbook/dysplasia.html Approach to Skeletal Dysplasias] |
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*[http://www.restrictedgrowth.co.uk Restricted Growth Association UK] |
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*[http://www.lpaonline.org Little People of America] |
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*[http://www.littlepeoplethebook.com <I>Little People: A Father Reflects on His Daughter's Dwarfism — and What It Means to Be Different</I>], by Dan Kennedy. Critically acclaimed book in a free online edition. |
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*[http://www.blogsmonroe.com/disability/ What is Normal?]Raising a child with Achondroplasia, a form of dwarfism by Tonya Sweat |
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*[http://medsapiens.com/achondroplasia_overview.html Information about achondroplasia] |
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{{Osteochondrodysplasia}} |
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[[Category:Genetic disorders]] |
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[[Category:Growth disorders]] |
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[[de:Achondroplasie]] |
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[[el:Αχονδροπλασία]] |
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[[es:Acondroplasia]] |
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[[fa:آکندروپلازی]] |
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[[fr:Achondroplasie]] |
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[[gl:Acondroplasia]] |
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[[ko:연골무형성증]] |
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[[it:Acondroplasia]] |
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[[nl:Achondroplasie]] |
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[[pl:Achondroplazja]] |
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[[pt:Acondroplasia]] |
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[[ru:Ахондроплазия]] |
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[[sl:Ahondroplazija]] |
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[[sr:Ахондроплазија]] |
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[[fi:Akondroplasia]] |
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[[tr:Akondroplazi]] |
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Revision as of 18:41, 26 September 2008
Acho