Achondroplasia: what is it? Symptoms and Treatment

Achondroplasia is the most common of birth defects, which are characterized by abnormal body proportions: from people suffering from this disease, there are signs of a relative macrocephaly (forehead projects forward and flat nasal bridge), hands and feet very short, with the legs and spine twisted, shoulder and thighs shortened more than the beam, and the torso is almost normal size.

Sometimes a big head is a reflection of hydrocephalus - the presence of excess fluid in the brain - and requires surgery. Palm in patients with achondroplasia are small with short, thick fingers. there is some distance between the middle and ring fingers (trident hand). In most cases, people are reaching adulthood, are the growth of not more than 120-130 cm.

What it is?

Achondroplasia - a genetic disease that results in a disorder of bone growth. This is one of the most common types of dwarfism. To judge the presence of a child of this disease can be from the moment of birth.

Pathogenesis and genetics

Achondroplasia is caused by mutations in the FGFR3 gene, and is in the fourth chromosome. At the same time it inhibits the growth of cartilage. FGFR3 encodes a protein called fibroblast growth factor 3. This protein is responsible for the growth of the body's bones. FGFR3 in achondroplasia may not work properly, and the growth of bone, cartilage is slowing down. This leads to short bones, abnormal shape of the bones, and low growth.

FGFR3 - transmembrane receptor tyrosine kinase that binds to FGF. Communication FGF from the extracellular domain of FGFR3 receptor activates the intracellular domain and triggers a signal sequence. In endochondral bone FGFR3 activation inhibits proliferation of chondrocytes in the growth plate, thus helping to coordinate growth and differentiation of chondrocytes with the growth and differentiation of progenitor cells bones.

Associated with achondroplasia FGFR3 mutations - mutations enhancing the function of causing ligand-independent activation of FGFR3 protein. This constant activation of FGFR3 protein improperly inhibits chondrocyte proliferation in growth plate and leads to a shortening of the long bones, and abnormal formation of other bones.

Guanine at position 1138 in the FGFR3 gene - one of the most mutated nucleotides identified in all human genes. The mutation of the nucleotide found in nearly 100% of cases of achondroplasia; with more than 80% of patients have a new mutation. New mutations of guanine in 1138 position FGFR3 gene occur only in the paternal germ cells, and their frequency increases with the father's age (> 35 years).

The symptoms of achondroplasia

Immediately after birth, you can discover the most obvious signs of achondroplasia in the newborn:

1. The deep location of the eye orbits,
2. The presence of additional folds at the inner corners of the eyes,
3. Saddle flattened shape of the nose,
4. Enlarged head,
5. Prominent forehead,
6. Markedly bulging parietal and occipital protuberance,
7. Wide-set eyes,
8. Hydrocephalus,
9. Strongly exposed buttocks due to the position of the pelvis backwards,
10. A small chest,
11. Enlarged tonsils,
12. Breathing problems
13. Violation of muscle tone,
14. Significant performance maxillary
15. High sky,
16. Coarse language,
17. Short arms and legs of the baby,
18. Broad hands and feet with short fingers,
19. The lag in physical development,
20. Possible torticollis,
21. Hearing and visual impairment.

With the growth of all these symptoms progress, which leads to multiple health complications, many of which are fraught with a fatal outcome.

diagnosis of achondroplasia

To assess the state of organs and systems is carried out a comprehensive survey. To exclude hydrocephalus children with achondroplasia conducted MRI brain CT.

1. When the X-ray of the skull in patients with achondroplasia there is a disproportion between the brain and the front part, the foramen magnum reduced in size, the bones of the cranial vault and mandible increased. Ephippium bashmakoobraznoy characteristic shape and flat, elongate base.
2. When X-rays of the spine gross changes usually are not detected. Physiological curves less pronounced than normal.
3. Chest radiography is usually unchanged, in some cases, the sternum protrudes slightly curved. Possible deformation and thickening of the edges. Sometimes there are no anatomical curves of the clavicle.
4. On the X-ray of long bones revealed shortening, thinning of the diaphysis, cup-shaped extension and thickening metaphyses.
5. In radiography joints revealed a deformation of the articular surfaces, impaired epiphyses shaped expansion joint gaps.
6. Pelvic radiography reveals resizing forms iliac wing. It is determined by the horizontal arrangement of the roof of the acetabulum.

Typically, diagnosis posing no difficulties due to the characteristic appearance of patient body proportions.

Achondroplasia - treatment

Effective treatment of achondroplasia currently not possible. Doctors can only minimize the effects to improve the quality of life of patients.

In children, for these kids is conducted conservative therapy - massage, physiotherapy. This helps strengthen the muscular system and prevent a strong deformation of the lower extremities. Patients are advised to wear special shoes, which reduces the pressure on the bone. It is also important to diet in order to avoid burdening the skeleton overweight. Defects in the jaw area are corrected by wearing special plates.

There are cases where in childhood prescribe hormone therapy, which allows slightly compensate for the lack of growth. Adult hormone therapy does not apply. If parents decide on a surgical solution to the problem, in case you need to refer to a specialist clinic that has adequate experience of such operations.

• Surgical intervention is carried out in the event that the disease brings obvious discomfort to the patient. Unequivocal decision in favor of the operation is taken under the threat of infringement of the spinal cord, kyphosis occurs, middle part of the back, "O" -shaped legs form.
• It is also possible lengthening of bones, which is several surgical interventions in phases. At the age of four to six years old children do surgery for leg lengthening (up to six cm), thighs (about seven-eight cm) and shoulders (a possible result - five centimeters). The duration of these stages - about five months with a break in two to three months. The next series of intervention carried out at the age of fourteen or fifteen years old. Here, the patient also goes through three stages, the expected result is the same as the first time.

However, such actions do not completely eliminate the disease and its symptoms, since the a small increase in the elongation of bones, even up to ten centimeters does not make patients look like ordinary people. In addition, not all patients are willing to undergo a number of operations and painful rehabilitation periods.

inheritance of achondroplasia

For healthy parent child with achondroplasia, the risk of recurrence in future children is low, but probably slightly higher than for the general population, as proved the possibility of sexual mosaicism, although extremely rare in Ahonen-droplazii.

In marriage, when one partner is sick achondroplasia, the risk of recurrence in each child is 50%, because achondroplasia - autosomal dominant disease with complete penetrance. In marriage, two patients each child has a 50% risk of having achondroplasia, 25% of the risk of a lethal homozygous achondroplasia, and a 25% chance of normal growth.

In pregnancy, a mother with achondroplasia necessary cesarean delivery is the result of normal growth.

prevention

Prevention of achondroplasia is the medico-genetic counseling and prenatal diagnosis, which can detect disease at the stage of fetal development. Consultation genetics is especially needed for those who are already in the family, there are cases of dwarfism. Special surveys will assess the patient's risk of giving birth.

If parents already have achondroplasia, the disease can not be prevented because it is inherited.