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Achondroplasia is a genetic, developmental disorder of the bones and cartilage that results in short stature, lumbar lordosis (sway-back), and limited elbow extension (Brown 2003, Moutou 2003). Commonly called dwarfism, this disorder has several other associated features, including delayed motor development; however, mental retardation is not associated with this disorder (Moutou 2003). Affected individuals will also have a small foramen magnum (the large hole located in the base of the skull which allows passage of the spinal cord); this can lead to cervicomedullary compression, which may cause infants to have difficulty breathing and sleeping (Moutou 2003, Jones 1997).
This disorder has been found to be autosomal dominant with the vast majority of the cases occurring spontaneously (Jones 1997). Achondroplastic parents have a 50% change of passing this disorder onto their children. If both parents have achondroplasia, then there is a 25% chance that the child will be homozygous for this disorder (Gooding 2002). Children who are homozygous for this disorder are much more severely affected than children who are heterozygous. The homozygous condition is almost always fatal within a few months after birth (Gooding 2002).
Approximately 80% of individuals with achrondroplasia have a mutation of fibroblast growth factor receptor 3 (FGFR3) (Su 2004, Li 2004, Brown 2003, Pehlivan 2003). This condition can be detected by genetic testing (amniocentisis or chorionic villi sampling), increased nuchal translucency on ultrasound, or using size-fractioned DNA in maternal plasma (Tonni 2005, Li 2004, Li 2002).
DEMOGRAPHIC AND REPRODUCTIVE FACTORS
Affected parents have a 50% chance of having offspring affected with this disorder, and a 25% chance of having a child that is homozygous for this disorder (Gooding 2002) but unaffected otherwise. They also have a 25% chance of having an unaffected child. The recurrence risk for this defect is dependent on whether or not the parents are affected. The recurrence risk for unaffected couples is low (Gooding 2002). One study indicated that the recurrence risk for unaffected couples that have one child with achondroplasia is 0.02% (Mettler 2000).
Advanced paternal age has been linked to this disorder in several studies (Wyrobek 2006, Kuhnert 2004, Glaser 2004, Rolf 2001,Orioli 1995). Achondroplasia has not been linked to advanced maternal age.
Paternal grandparents of children with achondroplasia tend to have higher risk for various types of cancer than do maternal grandparents, leading to a hypothesis of the existence of a "mutator" gene acting in male meiosis and in somatic, mitotic cells in both sexes which may favor also the occurrence of cancer (Stoll 2004).
It has also been suggested that achondroplasia occurs concurrently with polyhydramnios (an excess of amniotic fluid). Polyhydramnios in conjunction with achondroplasia can exacerbate the limb-shortening effect of this disorder (Latini 2002).
Achondroplasia is found in both males and females of all races/ethnicities. Prenatal diagnosis of this disorder by sonogram is not always successful (Parilla 2003).
FACTORS IN LIFESTYLE OR ENVIRONMENT
As achondroplasia is primarily a genetic disorder, there are no known teratogens for this disorder. Listed below are some common exposures that have been studied for increased risk of achondroplasia, but for which no association has been found:
- Maternal obesity (Cedergreen 2004)
- Maternal diabetes (Becerra 1990).
- Living in proximity to landfills or solid waste incinerators (Harrison 2003, Cordier 2004)
- Exposure to nitrate or chlorination byproducts in drinking water (Cedergren 2002) Marijuana and methamphetamines (Fried 2002, Jeng 2005)
- Chemotherapy (Cardonick 2004),
- Fluoxetine (Prozac™) (Chambers 1996)
- Anticonvulsant drugs (Holmes 2001).
- Antihistamine drugs (Kallen 2002).
- Corticosteroids and calcium channel blockers (Park-Wyllie 2000, Sorensen 2001).
- Thalidomide (Stromland 2002).
In Texas, the rate for achondroplasia is 0.32 per 10,000 live births.
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