Gnathodiaphyseal dysplasia is a hereditary disease of the skeleton characterized by a predominant lesion of the lower jaw in combination with the fragility of other bones. The symptoms of pathology are frequent fractures in childhood with the development of ossifying periodontitis and frequent purulent osteomyelitis of the jaws in the second to third decade of life. Diagnosis of gnathodiaphyseal dysplasia is performed by analyzing the clinical picture and anamnesis of the patient’s life, as well as molecular genetic techniques. There is no specific treatment for the disease.
Gnathodiaphyseal dysplasia is a genetic pathology that leads to fragility of the bones of the skeleton and disruption of the healing and ossification processes of the lower jaw. For the first time this disease was described in 1969 by the Japanese researcher Akasaka, who revealed an increased frequency of purulent osteomyelitis of the upper and lower jaw in the 21st representative of the same family. Upon further examination, it was found that each of the patients in childhood often suffered from bone fractures. In adulthood, fractures occurred less frequently, but there were pathologies of the lower jaw, sometimes with facial disfigurement. Further studies revealed similar disorders in representatives of the Negroid race. It was possible to determine that gnathodiaphyseal dysplasia is inherited by an autosomal dominant type, but it is extremely rare, so its prevalence has not yet been determined. Only in 2004, Japanese geneticists Masuko and Masaro Kato identified the localization of a gene whose mutations lead to this disease.
The direct cause of gnathodiaphyseal dysplasia is mutations in the ANO5 gene located on the 11th chromosome. It encodes the sequence of protein 16E, which is a transmembrane protein from a group of calcium channels capable of regulating almost all calcium metabolism in the cell. In addition to gnathodiaphyseal dysplasia, other mutations in the ANO5 gene can cause diseases such as Myoshi muscular dystrophy and lumbar-limb muscular dystrophy. Thus, these pathologies are allelic in relation to gnathodiaphyseal dystrophy. The reasons why the bulk of the lesion in this disease falls on the jaw bones are currently unknown. Mutations of the ANO5 gene are transmitted, leading to the development of this disease, according to the autosomal dominant type.
The pathogenesis of gnathodiaphyseal dysplasia is also currently being discussed in the scientific world. It is assumed that a missense mutation in the 11th exon of the ANO5 gene leads to a change in the transmembrane protein, which, in turn, complicates the mineralization processes due to a violation of calcium transport. As a result, the structure of all bones is disrupted (a decrease in the thickness of the cortical layer, sclerosis of the diaphysis of long tubular bones, a decrease in the overall density of bone tissue). In addition, in adulthood, there is a violation of bone metabolism in the upper and lower jaw. Therefore, purulent osteomyelitis often occurs, in place of which, after recovery, normal bone is not restored, but dense fibrous tissue with varying degrees of saturation of the cementing mass is formed. Similar changes occur not only after osteomyelitis, but also due to fractures of the jaw bones.
At birth and in childhood, patients with gnathodiaphyseal dysplasia are no different from healthy peers – growth, weight gain, and psychophysical development remain within normal limits. Approximately from the age of 12-13 years, the density of bone tissue begins to fall, but this does not manifest itself outwardly. But traumatic situations typical for a child (falls, outdoor games and others) often end in fractures. Cases are described when a teenager suffering from gnathodiaphyseal dysplasia under the age of 20 suffered several dozen fractures of various bones. However, there are usually much fewer of them, so parents rarely pay attention to the somewhat increased traumatism of their child, considering it a coincidence. An orthopedist or radiologist on fracture images may pay attention to a slightly reduced bone density, but in extremely rare cases correlates them with some kind of hereditary pathology. The fusion of fractures occurs in the usual time and without various complications.
Upon reaching the age of 20, patients with gnathodiaphyseal dysplasia often have purulent osteomyelitis of the upper and lower jaw with their typical symptoms – fever, symptoms of general intoxication, severe pain. At this stage, complications such as metastatic transfer of purulent inflammation, toxic shock, sepsis may develop. With the successful completion of the purulent process, bone tissue healing occurs with an anomaly – coarse fibrous tissue with hypercementosis is formed, corresponding to ossifying periodontitis. With frequent cases of osteomyelitis or fractures of the jaw bones, as a result of such improper regeneration, facial disfigurement may develop. In adulthood, with gnathodiaphyseal dysplasia, the fragility of other elements of the skeleton decreases, so the frequency of fractures decreases.
Diagnosis of gnathodiaphyseal dysplasia is made on the basis of X-ray examination of the jaw bones and other skeletal elements, the patient’s life history, molecular genetic analyses. On the X-ray of the lower and upper jaw, foci are determined, sometimes multiple, corresponding to the transferred osteomyelitis. They are slightly more transparent than the surrounding bone tissue (due to the presence of connective tissue there), but there are areas of compaction in them that are hypercementosis. Sometimes, in advanced cases of gnathodiaphyseal dysplasia, deformities of the upper or lower jaw are noted. Radiographs of other bones, especially those taken in adolescence and young age, show a decrease in the thickness of the cortical layer and a decrease in the overall bone density. An indirect sign of gnathodiaphyseal dysplasia is the presence of traces of numerous fractures.
A large number of injuries with bone fractures in childhood and adolescence are also noted in the patient’s life history or during his questioning. Genetic diagnosis is reduced to sequencing the sequence of the ANO5 gene or only its 11th exon. This makes it possible to detect a missense mutation, which is the cause of gnathodiaphyseal dysplasia. In addition, modern genetics allows for prenatal diagnosis of this disease, the material for the study can be taken by amniocentesis. Differential diagnosis of gnathodiaphyseal dysplasia should be performed with hereditary and acquired forms of osteoporosis and disorders of bone tissue development.
Treatment and prognosis
There is no specific treatment for gnathodiaphyseal dysplasia. If this disease was diagnosed in childhood, then during puberty, calcium and vitamin D preparations can slightly increase bone density and reduce the risk of fractures. However, such treatment should be prescribed only by a doctor, since there is a possibility of developing hypervitaminosis D. In addition, it is desirable to protect the patient from outdoor games, sports and other traumatic factors at least for the period from 12 to 18 years – the period of greatest bone fragility in gnathodiaphyseal dysplasia. At the first signs of osteomyelitis (pain in the upper or lower jaw, malaise, fever), it is necessary to urgently consult a doctor. Timely treatment of purulent inflammation will reduce its severity and avoid a number of complications.
The prognosis of gnathodiaphyseal dysplasia regarding recovery is extremely unfavorable. As for the threat to the patient’s life, it can be caused by severe fractures in childhood and adolescence, as well as complications of purulent osteomyelitis. In most cases, patients live to an advanced age, especially with timely access to a doctor for various pathological processes. Sometimes facial disfigurement may occur due to deformities of the jaw bones, which can be eliminated by plastic surgery.