Atelosteogenez – group of genetic pathologies-hondrodisplazy which often lead to a lethal outcome at early age or at a stage of pre-natal development. As the main displays of diseases a hypoplasia of femoral and humeral bones in their disteel departments, shortening of edges and narrowing of a thorax, dislocations of joints and a curvature of tubular bones act. Diagnostics of an atelosteogenez is made on the basis of a radiological picture of bone structures, the present status of the patient, results of genetic researches. Treatment of any form of an atelosteogenez does not exist today.
Atelosteogenez (de la Shapel's dysplasia, neonatal bone dysplasia) is a form of a lethal hondrodisplaziya which is characterized by high mortality at early age. The most common form of pathology ( the 2nd type) is inherited on the autosomno-recessive mechanism. Types of a disease of the 1st and 3rd types are caused by the mutations inherited on autosomno-prepotent type, but most often genetic damages of de novo are the reason of such atelosteogenez. Occurrence rather low – no more than 1:1 000 000, with identical probability a disease arises both at boys, and at girls. Isolated cases when patients lived up to adult or old age are known, the vast majority of them suffered atelosteogenezy the 2nd type and only one – a disease of the 3rd type. In pediatrics it is considered one of the most severe forms of congenital hondrodisplaziya.
Reasons of an atelosteogenez
Mutations in FLNB genes (the 1st and 3rd types) and SLC26A2 (the 2nd type) are the reason of an atelosteogenez. FLNB gene located on the 3rd chromosome codes protein under the name In which participates in creation of an intracellular framework, enters into numerous structures of connecting fabrics. The forms of an atelosteogenez caused by damage of this gene are characterized by autosomno-prepotent type of inheritance, but, considering a high lethality of such mutations, their spontaneous versions meet more often. Because of violation of structure of protein of a filamin In there are numerous anomalies of a skeleton, connecting fabrics, internals which often lead to pre-natal death of a fruit or death at early age.
Atelosteogenez of the 2nd type caused by SLC26A2 gene mutation is characterized by autosomno-recessive type of inheritance. This gene located on the 5th chromosome codes structure of the protein carrier sulfate of ions playing a key role in formation of proteoglikan of cartilaginous tissue. Also he participates in formation of endokhondralny types of bones therefore at violation of structure of this protein there are anomalies of development of the bone and muscular device characteristic of an atelosteogenez. In addition, various violations in formation of internals – a hypoplasia of lungs, congenital heart diseases are possible. All this leads to the fact that patients atelosteogenezy the 2nd type quite often die at early age.
Classification of an atelosteogenez
Now allocate three main types of a disease:
Atelosteogenez of the 1st type is caused by a lethal mutation of a gene of FLNB, de novo in most cases arising. Is the heaviest anomaly of development, in many cases leading to antenatalny death of a fruit.
Atelosteogenez of the 2nd type (de la Shapel's dysplasia) is called by a mutation of a gene of SLC26A2 which is transferred on the autosomno-recessive mechanism. Antenatalny or perinatal death at this form meets seldom, in most cases patients die in the first months or years of life of dysfunction of internals.
Atelosteogenez of the 3rd type is also caused by a mutation in a gene of the FLNB which is transferred on the autosomno-prepotent mechanism or arising spontaneously. Death usually comes in the first weeks of life from a heavy underdevelopment of some bodies.
In most cases , being based only on the data of survey of the patient and a radiological picture, it is not capable to differentiate separate types of an atelosteogenez. Only the doctor geneticist by means of a sekvenirovaniye of the sequences of the genes associated with a disease and definitions like mutation can make it.
Symptoms of an atelosteogenez
Symptoms of a disease are characterized by a certain variability. In most cases at sick newborns shortening of the top and lower extremities, reduction of the sizes of a thorax, assignment of thumbs on hands and legs are observed. The person often flat, on it is found the expressed gipertelorizm, zapadeny nose bridges and backs of a nose. At newborns the hypoplasia of pulmonary fabric also comes to light, quite often there are heart diseases and a stenosis of a throat which often and are a cause of death. If patients atelosteogenezy do not die in the first days and weeks of life, then subsequently the expressed scoliosis, ekvinovarusny deformation of foot, a clubfoot is diagnosed for them. Death at more advanced age also comes from the accompanying violations of internals.
Diagnostics and treatment of an atelosteogenez
Diagnostics of an atelosteogenez is made on the basis of assessment of the present status of the patient, these radiographic researches and by means of methods of modern genetics. At the same time on roentgenograms the curvature of long tubular bones, lack of the centers of ossification on their disteel sites is found. In x-ray pictures of bodies of a thorax shortening and violation of ossification of edges, change of shapes of chest vertebras, existence in their bodies of crevices comes to light. During survey dislocations of knee, coxofemoral and shoulder joints often are found. Ossification of bones of a brush is broken.
Genetic methods of diagnostics of an atelosteogenez come down to a sekvenirovaniye of the sequence of genes of FLNB and SLC26A2 for the purpose of identification and definition like mutations. Differential diagnostics should be made with other forms of hereditary neonatal displaziya (a diastrofichesky dysplasia, Larsen's syndrome). Also prenatal diagnostics of an atelosteogenez by means of ekhografichesky or genetic (amniocentesis) methods is possible.
Specific etiotropny treatment of any form of an atelosteogenez does not exist for today. The supporting treatment comes down to resuscitation postnatal actions, in certain cases – to surgical interventions for the purpose of correction of heart diseases or other internal violations. The forecast is extremely adverse, some percent of patients atelosteogenezy live up to age of one year, isolated cases when patients lived up to adult age are described.