Kraniometafizarny dysplasia – the hereditary state from group of osteokhondrodisplaziya which is characterized by anomalies of development of a skull and metafiz of bones of extremities. Symptoms of this disease are the gipertelorizm, malformations of the person which are quite often spoiling the patient, abnormal formation of the nasal courses with violation of their passability, sometimes headaches and curvatures of extremities. Diagnosis of a kraniometafizarny dysplasia is performed on the basis of studying of the present status of the patient, radiological yielded and results of molecular and genetic researches. Specific treatment of this pathology does not exist, use symptomatic therapy, in certain cases carry out surgical interventions for simplification of breath of the patient and improvement of its appearance.
Kraniometafizarny dysplasia – group of hereditary diseases which lead to malformations of bones of front and brain departments of a skull of various degree of expressiveness in combination with anomaly of metafiz of long tubular bones and other violations. Earlier this state was carried in one group with Payl's disease (a multiple metafizarny dysplasia, a kraniometafizarny dysplasia of Payl), however now it is allocated in separate nosological unit. It is connected with the fact that at this disease anomalies of a structure of a skull are prevailing (deformations, giperostoza and scleroses of bones) whereas pathologies of other departments of a skeleton are expressed poorly. There are two main forms of a kraniometafizarny dysplasia differing among themselves in the inheritance mechanism (autosomno-prepotent and autosomno-recessive types), clinical manifestations and expressiveness of violations. Due to inheritance by means of autosomes pathology with an equal share of probability affects both men, and women. Occurrence of a kraniometafizarny dysplasia is definitely not established, the prepotent type is registered many times more often than recessive.
Reasons of a kraniometafizarny dysplasia
Mutations in ANKH gene which is settling down on the 5th chromosome become the main reason for more frequent, but easier autosomno-prepotent form of a kraniometafizarny dysplasia. The gene codes protein which is a membrane carrier of the pyrophosphate participating in oppression of processes of calcification of a bone tissue and its resorption. As a result of genetic defect at protein carrier the structure changes, and it becomes incapable to perform fully the functions that leads to a kraniometafizarny dysplasia. At the cellular level it is shown by abnormal change of activity of osteoklast, development of a sclerosis and giperostoz mainly of skull bones. Also the configuration of the main openings of the basis of a skull can be broken that becomes the reason of a compression of some vessels and nerves and in many respects defines other symptoms of a kraniometafizarny dysplasia (a hearing disorder, headaches, damages of trigeminal and facial nerves). In genetics also other diseases caused by defeat of a gene of ANKH, in particular – hereditary pseudo-gout or family are known.
Much more rare autosomno-recessive form of a kraniometafizarny dysplasia is caused by defect of a gene of GJA1 localized on the 7th chromosome. A product of its expression is protein under the name 43, taking active part in formation of intercellular (interslot-hole) contacts in many fabrics that allows cages to exchange low-molecular connections. The pathogenesis of development of a kraniometafizarny dysplasia at c716G missens-mutation> is unknown to A, the main problem comes down to identification of the reasons of the isolated damage of bones of a skull and metafiz of bones at relative absence of pathologies of other bodies. Considering that the greatest number of a konneksin 43 at the person is in heart fabric, the question of absence of pathologies of heart at this mutation represents a riddle for most of doctors geneticists today. As well as in case of an autosomno-prepotent form of a kraniometafizarny dysplasia, at this type of a disease the numerous secondary violations caused by impact of the changed bones and openings on nervous structures are observed.
Symptoms of a kraniometafizarny dysplasia
Autosomno-dominantny the type of a kraniometafizarny dysplasia is characterized by easier current, quite often at the birth of the child no symptoms of a disease come to light. Only by first year of life there is a gipertelorizm with expansion of a nose bridge owing to a giperostoz of nasal bones. Further the kraniometafizarny dysplasia leads to narrowing of the nasal courses and violation of their passability therefore at patients the mouth because of the broken nasal breath is quite often slightly opened. By 6-7 years increase in metafiz of long tubular bones can begin to be defined that is externally shown by increase in the sizes of knee and elbow joints. Approximately at a half of patients with a kraniometafizarny dysplasia a hearing disorder of various expressiveness up to full deafness develops – most often it is caused by a compression of an acoustical nerve in the bone channel. Because of a sdavleniye of nerves there are also other neurologic violations, disorders of sensitivity on a face, neuralgia of a trigeminal nerve and headaches are possible.
The Kraniometafizarny dysplasia of autosomno-recessive type is characterized by much more more expressed malformations of bones of a skull and extremities, symptoms of pathology often come to light right after the child's birth. Patients have an expressed gipertelorizm, features are often extremely asymmetrical, deformations of a nose bridge and a nose can get ugliness signs. In some cases the makrotsefaliya, a mandibular prognatizm, other violations of a bite and arrangement of teeth are observed. In process of growth of the patient of anomaly of bones of a skull can be aggravated. Metafiza of bones of extremities are sharply expanded that quite often causes secondary deformations (for example, a H-shaped curvature of legs). As well as in the previous option, at this form of a kraniometafizarny dysplasia often there are various neurologic violations caused by a sdavleniye and a travmatization of craniocereberal nerves. They can be shown by deafness, sight violations, disorders of skin sensitivity on a face, paresis of mimic muscles and headaches. There are separate descriptions of the patients who at the same time have a kraniometafizarny dysplasia and intellectual backwardness, however there are no reliable data about interrelation of these two states today.
Diagnostics and treatment of a kraniometafizarny dysplasia
Diagnosis of a kraniometafizarny dysplasia is based on data of survey of the patient, studying of its hereditary anamnesis, results of radiological researches and molecular and genetic analyses. At survey anomalies of development of bones of a skull, various on expressiveness, are defined that affects features of the patient. At the same time the autosomno-prepotent form, especially at small children, quite poorly proves concerning this symptom. At both types of a kraniometafizarny dysplasia practically there are always a gipertelorizm, expansion of a nose bridge due to growth of nasal bones towards cheekbones, narrowing or impassability of the nasal courses. Within fizikalny survey and additional researches neurologic violations can be also revealed: decrease or lack of hearing, decrease in sight, symptoms from trigeminal and facial nerves.
Much more information at a kraniometafizarny dysplasia is given by radiological methods of a research of a skeleton. On roentgenograms of a skull at an autosomno-prepotent form of a disease consolidation of a bone tissue in an occipital bone, the skull basis sclerosis, the lowered pnevmatization of sine and cells of a temporal bone are defined. In some cases the sclerosis of interosseous seams and expansion of metafiz of tubular bones can come to light. At autosomno-recessive type of a kraniometafizarny dysplasia on roentgenograms the similar, but much more more expressed violations, for example – total absence of okolonosovy bosoms, sharp narrowing and sometimes filling with a bone tissue of openings of craniocereberal nerves are found. Besides, the sclerosis not only the bases is observed, but also the skull arch, in some cases considerable deformations of bones of front department are defined. Is a little stronger, than at prepotent type, expansion and a sclerosis of metafiz of tubular bones are expressed.
Studying of the hereditary anamnesis and genetic diagnostics are also actively used for definition of a kraniometafizarny dysplasia. At the same time it is possible to establish at first type of inheritance of a disease that allows to correct the molecular and genetic analysis for search of mutations in a concrete gene. For this purpose apply a method of a direct sekvenirovaniye of genes of ANKH and GJA1.
Specific treatment of a kraniometafizarny dysplasia does not exist, appoint symptomatic therapy with attraction various surgical the technician. The last, in particular, can improve passability of the nasal courses for breath simplification. It is possible to reduce expressiveness of neurologic symptomatology by expansion of openings of the corresponding craniocereberal nerves. Besides, plastic surgeons are capable to minimize expressiveness of esthetic defects at a kraniometafizarny dysplasia. For improvement of hearing use hearing aids.
Forecast and prevention of a kraniometafizarny dysplasia
In many cases the forecast of a kraniometafizarny dysplasia of autosomno-prepotent type concerning survival of the patient favorable – neither anomalies of a skull, nor secondary neurologic violations lead to serious consequences. The pathologies of hearing or sight arising in the childhood can slowly progress up to 20-30 years, after that deteriorations usually do not happen. Autosomno-retsessivny the type of a kraniometafizarny dysplasia is characterized by more adverse forecast as bone violations of a skull at this state tend to aggravation and can injure nerves more and stronger every year. In certain cases it leads to paralyzes and frustration from the autonomic nervous system. Prevention of a kraniometafizarny dysplasia is not developed, for reduction of risk of development of complications in the presence of such state it is necessary to conduct regular examination at the neurologist.