Achondroplasia is caused by a specific genetic mutation that affects the way cartilage is converted into bone during development. This mutation occurs in the gene known as FGFR3 (fibroblast growth factor receptor 3). Normally, FGFR3 plays a role in regulating bone growth by controlling how cartilage cells grow and mature. However, in achondroplasia, a mutation in this gene causes it to be overly active, which disrupts normal bone growth, especially in the long bones like the femur (thigh bone) and humerus (upper arm bone).
Because of this mutation, the cartilage that is supposed to turn into bone during fetal development and early childhood does not develop properly, leading to shorter limbs while the trunk of the body remains relatively normal in size. This is why individuals with achondroplasia have disproportionately short arms and legs compared to their torso. The mutation also affects the skull, causing an enlarged head with a prominent forehead and other characteristic facial features such as a flattened nose and a protruding jaw.
Achondroplasia is inherited in an autosomal dominant pattern, which means only one copy of the mutated gene is enough to cause the disorder. However, about 80 percent of cases arise from new mutations that occur spontaneously, without being inherited from a parent. This means that many children with achondroplasia are born to parents of average height who do not carry the mutation.
The mutation in FGFR3 leads to excessive signaling that inhibits the growth of cartilage cells, preventing them from multiplying and maturing as they should. This abnormal signaling causes the bones that rely on cartilage models for growth to remain short and misshapen. The disorder primarily affects the growth plates of long bones, which are the areas where new bone is formed during childhood.
Besides the short limbs, other physical features caused by the mutation include a curved lower spine, a narrow chest, and sometimes a narrow pelvis in females, which can complicate childbirth. Despite these skeletal abnormalities, individuals with achondroplasia usually have normal intelligence and overall good health.
Recent advances in medicine have focused on targeting the FGFR3 mutation to develop treatments that can improve bone growth and reduce complications. Some new drugs aim to block the overactive FGFR3 signaling, potentially allowing for increased growth in children with achondroplasia. These treatments are still being studied but represent a promising direction for managing the condition beyond traditional supportive care.
In summary, achondroplasia is caused by a mutation in the FGFR3 gene that leads to abnormal cartilage development and bone growth, resulting in the characteristic short stature and skeletal features of the disorder. Most cases are due to new mutations rather than inherited ones, and ongoing research is exploring ways to counteract the effects of this mutation to improve outcomes for affected individuals.
