The main difficulty in calculating the incidence of this disease is due to the fact that in more than 80% of cases it occurs spontaneously due to de novo mutations. The remaining proportion of cases of hypochondroplasia (less than 20%) is transmitted by an autosomal dominant mechanism. However, it is well established that this pathology is much less common than achondroplasia (1.20000), although it has a milder course. The disease is equally likely to buy orlistat online both men and women.
The great similarity of the manifestations of hypochondroplasia with achondroplasia is due to the fact that the cause of these diseases are mutations of the same gene - FGFR3, located on the 4th chromosome. It encodes the sequence of fibroblast growth factor-3, which is a transmembrane tyrosine kinase receptor. Normally, it somewhat inhibits the growth of fibroblasts and chondrocytes in the growth plates of endochondral bones, thereby controlling the proper development of bone tissue. With mutations in the FGFR3 gene, the resulting fibroblast growth factor-3 has a defect and cannot fully perform its functions - depending on the nature of the genetic defect, this can lead to thanatoform dysplasia, achondroplasia, or hypnosis.ochondroplasia.
Several dozen mutations of the FGFR3 gene have been identified, resulting in the development of dwarfism by the type of hypochondroplasia.
The most common is a defect that occurs due to order xenical of a nitrogenous base (adenine or guanine) at position 1620 of the thirteenth exon of the gene.
- As a result, asparaganine is replaced by lysine at position 540 in the protein derived from such a gene, which significantly changes the tyrosine kinase sensitivity of the receptor.
- In addition, many other substitutions of nitrogenous bases in the gene and, as a result, amino acids in the resulting protein, have been described, which lead to the development of symptoms of hypochondroplasia.
- However, there are indications that in some patients with the clinical picture of this disease, genetic testing did not reveal defects in FGFR3.
- This may indicate that other genes may also be involved in the development of hypochondroplasia.
All mutations of the above gene are inherited by an autosomal dominant mechanism, but in the vast majority of cases they are spontaneous and are not detected in the parents or relatives of the patient. It has been noted that in many patients with hypochondroplasia, the age of the fathers exceeds the average, which may indicate the germinal nature of the occurrence of FGFR3 gene mutations.
As a rule, in the first years of a child's life, hypochondroplasia does not manifest itself in any way - at birth there are no deviations from the norm, weight gain and psychophysical development occur normally. The first signs of growth retardation are recorded at the age of 3-4 years, a slight disproportion of the body becomes noticeable (short arms and legs, enlarged feet and hands). In many cases, people around do not even immediately identify any unusual proportions in patients - they just look like short, stocky people. The shape of the skull and facial features with hypochondroplasia are often without features, sometimes a slight brachycephaly can be detected.
Patients sometimes experience minor flexion contractures of the elbow joints and, very rarely, of the hip joints.
Valgus curvature of the femur with hypochondroplasia is not observed, similar deformities of the lower leg are possible. In about half of the cases, patients develop lordosis of orlistat pills. Since all these manifestations are similar to the symptoms of achondroplasia, only they are much less pronounced, for a long time it was believed that this is one and the same pathology, only some researchers attributed it to an independent nosological unit. Only modern research in the field of genetics has unambiguously proved the validity of such a selection of hypochondroplasia.
Identification of hypochondroplasia is made on the basis of a set of medical measures. consultations of a pediatrician and orthopedist, x-ray studies, molecular genetic analysis. When examining patients older than 3-4 years, changes characteristic of the pathology are found - shortened limbs, increased relative size of the feet and hands, mobility disorders in the elbow and sometimes in the hip joint, lumbar lordosis.