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Achondroplasia is a genetic disorder that affects bone growth and causes the most common type of dwarfism, being responsible for 70% of cases. It is included within a group of diseases called chondrodystrophies, or osteochondrodysplasias.
During fetal development and childhood, cartilage tissues normally become bones but in places like the nose and ears. In individuals affected by achondroplasia, this process is abnormally slow and results in short bones and short stature, especially in longer bones such as arms and legs. Therefore, affected individuals have very short arms and legs, though the torso remains practically normal in size. The average height of a male and a female with achondroplasia is approximately 1.31 m and 1.24 m, respectively.
The characteristic appearance of dwarfism caused by achondroplasia is seen from birth. These patients usually have a large head, a fairly prominent forehead, and a flattened bridge of the nose. The size of the head is sometimes larger due to hydrocephalus (excess fluid in the brain) and requires surgery. On the other hand, the hands are usually small, with a separation between the middle and ring fingers (also known as trident hand) and stubby fingers. The feet are usually short, wide, and flat. In addition, they tend to show low muscle tone and usually have spinal stenosis, as well as kyphosis and lordosis, which are types of abnormally curved spine.
Health problems associated with achondroplasia include breathing problems, usually apnea (breathing slows or stops for short periods), obesity, and ear infections. Older people often suffer from back pain.
Increased morbidity is observed in children with this disorder due to neurological complications they experience during the early years of life, but their intelligence is not affected.
There is no specific treatment or cure for achondroplasia, but many of its complications can be treated effectively. Children with this disease are usually under continuous monitoring of their development to treat any complications that may arise, such as hydrocephalus, spinal cord compression, etc. Sometimes surgery is done to remove the tonsils or adenoids (lymphatic tissue near the throat) to improve breathing problems. Other problems arising from this disorder, such as kyphosis (a deformation of the spine) can be corrected with braces. Similarly, to prevent hearing loss due to frequent infections, small drainage tubes are often placed in the middle ear.
Children suffering from achondroplasia usually gain weight from an early age, so nutritional monitoring is important to prevent further the problems in the bones.
Some research groups have evaluated the possibility of using human growth hormone to increase the height of affected children; however, this treatment has not shown significant results to date. There is the option of leg lengthening surgery, which in result increases the height of affected individuals, but it is controversial because it is a lengthy process that involves a number of possible complications. It is strongly recommended that these interventions be done at centers with a lot of experience in this type of treatment.
Achondroplasia is caused by mutations in the FGFR3 gene. This gene provides instructions for the formation of fibroblast growth factor receptor type 3, a protein that controls the growth of cartilage cells. Mutations in this gene result in decreased proliferation and growth of these cells, which later leads to decreased longitudinal growth of bones, producing the characteristic symptoms of the disease.
The incidence of this disorder ranges from one in 25,000 to one in 40,000 babies born, occurring in all races and in both sexes equally. In Spain, it is estimated that approximately 1,000 people are affected by achondroplasia.
Achondroplasia follows an autosomal dominant pattern of inheritance. This means that only one copy of the altered gene is sufficient for the disease to appear. However, 80% of cases are caused by de novo mutations, which occur when neither parent suffers from the disease and a mutation in the gene develops spontaneously. In addition, mutations can occur in the parents’ germ cells, that is in eggs and sperm. In these cases, the parents usually have normal height and the chances of having a child with this disease are very small. In the minority of cases, the child inherits the disorder from an affected parent. If one parent has the disease, there is a 50% chance that they will pass it to the child. If both parents have the disease, there is a 50% chance that the child will inherit one copy of the affected gene and develop the disease, 25% that they will not inherit it, and another 25% that they will inherit an altered copy of the gene from each parents and, as a result, suffer severe abnormalities in the skeleton and early death.