What is the pathogenesis of achondroplasia?
Achondroplasia is caused by mutations in the fibroblast growth factor receptor-3 (FGFR3) gene. Mutations within FGFR3 are the only genetic changes known to cause achondroplasia. FGFR3 has been mapped to the short arm of chromosome 4, p16.
Is achondroplasia dominant negative?
Achondroplasia (Ach) is the most common form of dwarfism in humans. It occurs with a frequency of 1 in 15–25,000 and 80% of cases are sporadic. Ach is an autosomal dominant genetic disease that has 100% penetrance.
Which zones are most affected by achondroplasia?
The thigh and upper arms are more affected because they have longer bones and larger growth plates (regions of the bones where growth occurs). The lower legs and forearms are affected to a lesser degree because their growth plates are smaller.
What are the characteristic features of achondroplasia?
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly ) with a prominent forehead .
What type of mutation is achondroplasia?
What is achondroplasia? Achondroplasia is caused by a gene alteration (mutation) in the FGFR3 gene. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone.
What is the role of FGFR3?
The FGFR3 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning of the protein allows it to interact with specific growth factors outside the cell and to receive signals that control growth and development.
What type of mutation causes achondroplasia?
Achondroplasia results from specific changes (mutations) of a gene known as fibroblast growth factor receptor 3 (FGFR3). For most patients, there is no apparent family history of the condition.
What organs are affected by achondroplasia?
Achondroplasia impairs the growth of bone in the limbs and causes abnormal growth in the spine and skull.
What are the specific symptoms of achondroplasia?
Achondroplasia Symptoms
- Shortened arms and legs, with the upper arms and thighs more affected than the forearms and lower legs.
- Large head size with a prominent forehead and a flattened nasal bridge.
- Crowded or misaligned teeth.
What causes achondroplasia?
This genetic disorder is caused by a change (mutation) in the fibroblast growth factor receptor 3 (FGFR3) gene. Achondroplasia occurs as a result of a spontaneous genetic mutation in approximately 80 percent of patients; in the remaining 20 percent it is inherited from a parent.
How is achondroplasia diagnosed?
Achondroplasia is diagnosed by characteristic clinical and X-ray findings in most affected individuals. In individuals who may be too young to make a diagnosis with certainty or in individuals who do not have the typical symptoms, genetic testing can be used to identify a mutation in the FGFR3 gene.
Which chromosome is affected in achondroplasia?
Although this condition can be inherited in an autosomal dominant manner, 80% of cases are due to new, sporadic mutations. Mutations involve the gene encoding fibroblast growth factor receptor 3 (FGFR3), situated on chromosome 4.
What type of receptor is FGFR3?
Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene. FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16. 3, is expressed in tissues such as the cartilage, brain, intestine, and kidneys.
What type of disease is achondroplasia?
Achondroplasia is the most common form of skeletal dysplasia, occurring in about one in every 40,000 births. Achondroplasia impairs the growth of bone in the limbs and causes abnormal growth in the spine and skull.
What was the first case of achondroplasia?
This form of dysplasia accounts for greater than 90% of cases of disproportionate short stature, also known as dwarfism. [1] The term “achondroplasia” was first used in 1878 to distinguish it from rickets, one of many other abnormal conditions of bone growth.
Where is the achondroplasia gene located?
Phenotype-Gene Relationships
| Location | Phenotype | Gene/Locus |
|---|---|---|
| 4p16.3 | Achondroplasia | FGFR3 |
What is FGFR3 function?