Achondroplasia is a type of autosomal dominant genetic disorder that is a common cause of dwarfism. Achondroplastic dwarfs have short stature, with an average adult height of 131 cm (4 feet 3.8 inches) for males and 123 cm (4 feet 0.6 inches) for females. An autosome is a non-sex chromosome. ... The word dominant has several possible meanings: In music theory, the dominant or dominant note (second most important) of a key is that which is a perfect fifth above the tonic; in just intonation the note whose pitch is 1. ... A genetic disorder is a condition caused by abnormalities in genes or chromosomes. ... This article is about the medical condition. ... People who are shorter have short stature. ... This article is being considered for deletion in accordance with Wikipedias deletion policy. ... A foot (plural: feet) is a non-SI unit of distance or length, measuring around a third of a metre. ...

The prevalence is approximately 1 in 25,000.^[1]

Causes

Achondroplasia is by far the most common chondrodysplasia in humans with an estimated prevalence to be one in 15,000 to 40,000 live births.[1] Achondroplasia is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 (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. It has been suggested that this article or section be merged into Dominance relationship. ... For linguistic mutation, see Apophony. ... NIH/3T3 Fibroblasts A fibroblast is a type of cell that synthesizes and maintains the extracellular matrix of many animal tissues. ... Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Cartilage is a type of dense connective tissue. ... FGFR3 is a fibroblast growth factor receptor that has been associated with several conditions, including: achondroplasia/hypochondroplasia thanatophoric dwarfism seborrheic keratosis[1] bladder cancer[2] ^ Hafner C, Hartmann A, Vogt T (2007). ...

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.^[2] Individuals in the mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes. ... For linguistic mutation, see Apophony. ...

New gene mutations are associated with increasing paternal age^[3] (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. Cross section of the epithelium of a seminiferous tubule showing various stages of spermatocyte development Spermatogenesis is the process by which male spermatogonia develop into mature spermatozoa. ... In medicine (genetics), a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one patient, where usually one of the two is affected by a genetic disorder. ... FGFR3 is a fibroblast growth factor receptor that has been associated with several conditions, including: achondroplasia/hypochondroplasia thanatophoric dwarfism seborrheic keratosis[1] bladder cancer[2] ^ Hafner C, Hartmann A, Vogt T (2007). ... A nucleotide is a chemical compound that consists of 3 portions: a heterocyclic base, a sugar, and one or more phosphate groups. ... For the plant, see Glycine (plant). ... Arginine (abbreviated as Arg or R)[1] is an α-amino acid. ...

There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia. Hypochondroplasia is a developmental disorder caused by an autosomal dominant genetic defect in the fibroblast growth factor receptor 3 gene (FGFR3) that results in a disproportionately short stature, micromelia, and a head that appears large when compared with the underdeveloped portions of the body. ... Thanatophoric dysplasia is a severe inherited skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs. ...

Diagnosis

Achondroplasia can be detected before birth by the use of prenatal ultrasound. A DNA test can be performed before birth to detect 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. Prenatal diagnosis is the diagnosis of disease or condition in a fetus or embryo before it is born. ... For other uses, see Ultrasound (disambiguation). ... Genetic fingerprinting or DNA testing is a technique to distinguish between individuals of the same species using only samples of their DNA. Its invention by Sir Alec Jeffreys at the University of Leicester was announced in 1985. ... It has been suggested that this article be split into multiple articles accessible from a disambiguation page. ... A stillborn baby girl, Breanna Lynn Bartlett-Stewart, shortly after stillbirth. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ... Otitis media is inflammation of the middle ear: the small space between the ear drum and the inner ear. ...

Radiologic findings

A skeletal survey is useful to confirm the diagnosis of achondroplasia. Skull films 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,^[4] 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 double jointed. In anatomy, in the occipital bone, the foramen magnum (Latin: great hole) is one of the several oval or circular apertures in the base of the skull (the foramina), through which the medulla oblongata (an extension of the spinal cord) enters and exits the skull vault. ... The spinal canal is the space in vertebrae through which the spinal cord passes. ... The metaphysis is the body of cartilage that separates the epiphyses and the diaphysis of long bones during growth. ... For the ornamental clasp, see Fibula (brooch). ... The metacarpus is the intermediate part of the hand skeleton that is located between the fingers distally and the carpus which forms the connection to the forearm. ... The phalanges in a human hand The name Phalanges is commonly given to the bones that form fingers and toes. ... Radiography is the creation of radiographs, photographs made by exposing a photographic film or other image receptor to X-rays. ... Hypermobility (also called double-jointedness, hypermobility syndrome or hyperlaxity) describes joints that stretch farther than is normal. ...

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. For other uses, see Ultrasound (disambiguation). ... The femur or thigh bone is the longest, most voluminous, and strongest bone of the mammalian bodies. ...

Treatment

At present, there is no treatment for achondroplasia.

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 under gone, some affected individuals may experience their limbs becoming "locked to their torso".^[5] Growth hormone (GH) or somatotropin (STH) is a protein hormone which stimulates growth and cell reproduction in humans and other animals. ... Distraction osteogenesis, also called callus distraction[1], callotasis[1], osteodistraction[], is a surgical process used for the reconstruction of skeletal deformities and for the lengthening of bones (as limb lengthening or particularly leg lengthening when referred to the lower limbs). ...

Miscellanous

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).^[6]

References

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 332nd day of the year (333rd in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• Achondroplasia UK The Number one UK website with over 500 members.
• Description of Achondroplasia from the Wellcome Trust Human Genome site
• Genetics of Achondroplasia
• Achondroplasia by Kathleen Tozer, M.D. & Bart Keogh, M.D., University of Washington Department of Radiology
• Approach to Skeletal Dysplasias
• Restricted Growth Association UK
• Little People of America
• Little People: Learning to See the World Through My Daughter's Eyes, a book by Dan Kennedy
• What is Normal?Raising a child with Achondroplasia, a form of dwarfism by Tonya Sweat
• Information about achondroplasia