Kampomelichesky dysplasia – the lethal genetic disease from group of osteokhondrodisplaziya which is characterized by heavy skeletal anomalies and other violations which quite often lead to pre-natal death of a fruit or the death of the newborn in the first weeks of life. Symptoms of this state are the strong curvature of tubular bones of extremities, existence of 11 pairs of edges and bell-shaped deformation of a thorax. In some cases there is an inversion of a floor. Diagnosis of a kampomelichesky dysplasia is most often made on the basis of these prenatal ultrasonographies, a kariotipirovaniye and molecular and genetic researches, after the child's birth for confirmation can be used given to a X-ray analysis. Treatment of this genetic disease does not exist.
Kampomelichesky dysplasia (kampomelichesky dwarfism) – the genetic disease which is followed by numerous anomalies of a skeleton and violation of a sexual differentiation. For the first time pathology was described by the famous French pediatrician Pierre Maroto in the 1971st year, however long time the etiology and pathogenesis of this state remained unknown. Only in recent years methods of modern genetics succeeded to identify a gene which defects lead to development of a kampomelichesky dysplasia and to define the sequence of pathological processes at this state. Occurrence of pathology makes about 1 on 150-200 thousand newborns, however some researchers challenge these figures, pointing to the increased risk of prenatal death which is not considered by statistics. It is established that the kampomelichesky dysplasia is an autosomno-prepotent state, but practically always arises because of spontaneous mutations at an embryo or in gametes of parents. There are messages on several patients with this pathology who lived up to teenage age.
Reasons of a kampomelichesky dysplasia
At the beginning of studying of a kampomelichesky dysplasia of many doctors geneticists nonplused an unusual combination of violations – skeletal anomalies of extremities, shovels, edges and pathology of a skull (a crevice of a hard palate, a mikrotsefaliya) with a hermaphroditism and sexual inversion. The reason of so unusual combination was covered in a gene which mutations become a cause of illness – SOX-9 gene located on the 17th chromosome. The gene codes the protein of the same name which is one of the major transkriptsionny factors in a human body. For example, it controls work of a gene of Col2A1 which is localized on the 12th chromosome and codes the sequence of the main kind of collagen of the 2nd type which is taking part in processes of formation of a skeleton and an ossifikation. Defects in structure of a protein of SOX-9 lead to sharp decrease in an expression of a gene of Col2A1, deficiency of collagen and as a result – to a kampomelichesky dysplasia.
Other important SOX-9 function is activation of a gene of AMH which is located on the 19th chromosome. Generally this gene expressirutsya in Sertoli's cells at men in the course of an embryonal development. AMH codes the so-called the inhibiting factor which leads to destruction of Myullerov Canal playing an important role in a sexual differentiation of a fruit of myuller. At SOX-9 gene mutations this function is broken, as a result of about 75% of patients with a kampomelichesky dysplasia at a karyotype of XY female sexual characters have fenotipichesk. In the past because of discrepancy of a gentotip and a phenotype was considered that this disease affects girls much more often, than boys. Many researchers assume active participation of protein SOX-9 and in control of other genes what indirectly points existence of many other anomalies of development at a kampomelichesky dysplasia to.
Symptoms of a kampomelichesky dysplasia
At a kampomelichesky dysplasia rather often arises pre-or the intranatalny death caused by sharp respiratory insufficiency at the baby. When the patient is born live, the expressed deformation of long tubular bones of hands and legs, lengthening of a brain part of a skull with considerable reduction of front department, a mikrognatiya and the reduced body sizes are found. At patients with a kampomelichesky dysplasia the flat face comes to light, the crevice of a hard palate and congenital dislocation of a hip are quite often observed. At inspection a hypoplasia of shovels, deformations of feet, and various congenital heart diseases are also defined. The Kampomelichesky dysplasia leads to the death of the patient for the first days or weeks of life. As a rule, the lethal outcome comes because of expressed respiratory a distress syndrome, the contribution is made by malformations of a skull, urinary and cardiovascular systems.
Diagnostics and treatment of a kampomelichesky dysplasia
The main role in definition of a kampomelichesky dysplasia is played by techniques of prenatal diagnostics: ultrasonography, kariotipirovany and molecular and genetic analyses. By ultrasonic methods this disease can be revealed already from the 2nd trimester of incubation of the child, the curvature of bones of extremities, existence of 11 pairs of edges and a bell-shaped shape of a thorax will be the leading manifestations. Also malformations of a skull, person, heart and kidneys, a hypoplasia of shovels and bodies of vertebras, increase in the sizes of a pelvic opening can be defined. On the basis of the listed data of prenatal ultrasonography it is possible to assume reasonably existence of a kampomelichesky dysplasia and to raise a question of termination of pregnancy on medical indications.
Kariotipirovaniye is made for the purpose of an exception of aneuploidiya or chromosomal anomalies which can cause similar manifestations and malformations of a fruit. At the same time in case of a kampomelichesky dysplasia definition of a karyotype can indicate a fruit male whereas by results of ultrasonographies the girl is defined. It serves as additional confirmation of this disease as the hermaphroditism and sexual inversions are characteristic of it. For the most exact diagnostics molecular and genetic analyses can be used by method of a sekvenirovaniye of the sequence of a gene SOX-9. Detection of mutations in this gene is final confirmation of existence of a kampomelichesky dysplasia.
In certain cases diagnosis of a kampomelichesky dysplasia is made at the living newborn. For this purpose, besides the above-stated techniques, apply a radiological research of a skeleton. On roentgenograms numerous deformations of tubular bones and other signs which were revealed for ultrasonography are defined. Vrachi-neonatologi can also define at the newborn with a kampomelichesky dysplasia heart disease, anomalies of development of kidneys and respiratory violations. Quite often final confirmation of the diagnosis is made on the basis of data of a pathoanatomical research. Practical any medical actions, even palliative character, at this disease are inefficient and incapable to prolong the patient's life.
Forecast and prevention of a kampomelichesky dysplasia
As the kampomelichesky dysplasia is a lethal form of an osteokhondrodisplaziya with the accompanying violations, the forecast of this disease exclusive adverse. If the child manages to survive in the intranatalny period, the lethal outcome comes in the first weeks of life from respiratory and other violations. Separate messages on survival of patients with a kampomelichesky dysplasia up to teenage age are viewed in the scientific environment with skepticism. Prevention of this state, considering spontaneous character of mutations of a gene of SOX9, it is possible only within prenatal inspection. At identification at a fruit of a kampomelichesky dysplasia and confirmation of this diagnosis the question of termination of pregnancy on medical indications is raised.