Craniodiaphyseal dysplasia is a congenital skeletal disorder associated with hyperostosis and sclerosis in the facial skull. The cause is a genetic mutation of bone-building inhibitory genes. Therapy is symptomatic and focuses on halting disease progression.
What is craniodiaphyseal dysplasia?
In hyperostosis, bone substance multiplies in an abnormal way. Hyperostosis of the skull is a group of diseases related to such an increase in bone substance around the skull. As craniodiaphyseal dysplasia is characterized by congenital hyperostosis of the skull and belongs to skeletal diseases. Australian physician John Halliday first described the condition in the mid-20th century. The prevalence is reported to be less than one case in 1,000,000 people. This makes the skeletal disease an extremely rare dysplasia of the skull. Meanwhile, the complex of hyperostosis and stenosis of the facial and cranial bones has been attributed to a genetic cause. Due to the few documented cases so far, not all correlations of the disease have been conclusively clarified. For this reason, therapeutic options are also limited at the present time.
Causes
Craniodiaphyseal dysplasia occurs in a large number of cases not sporadically but with familial clustering. Both autosomal recessive and autosomal dominant inheritance have been identified as the mode of inheritance for the disease. In the autosomal dominant form, the disease is caused by a new mutation in the SOST gene. The gene is located at location 17q21.31 and is considered one of the major inhibitors of bone formation. Mutation of SOST genes is responsible for a variety of inherited bone diseases, such as VDB. When mutated, the gene can no longer fulfill its inhibitory functions and the bone structure proliferates. This fundamentally distinguishes the hyperostosis of craniodiaphyseal dysplasia from other hyperostoses. In fact, these diseases are usually based on a dysfunction of the osteoclasts or osteoblasts. The genetic disposition is considered to be established in connection with the disease. What other factors play a role in the onset of the disease has not been conclusively determined.
Symptoms, complaints, and signs
The clinical picture of craniodiaphyseal dysplasia is characterized by various clinical criteria that find manifestation as early as infancy. For example, affected infants usually have severely obstructed nasal passages, which can cause them breathing problems. In the later course of the disease, complete obstruction of the nasal passages occurs in most cases. Frequently, the patients’ tear ducts also become obstructed after this phenomenon. Progradient nasal bulges of bony substance form on the lower jaw of most affected individuals during the course of the disease. Hyperostosis of the facial skull progresses and develops into leontiasis ossea. Tooth development of patients is disturbed or delayed in most cases. The interior of the skull narrows increasingly as the disease progresses. The narrowing also affects the foramina and causes consecutive optic atrophy. Accompanying symptoms may include hearing loss and more or less severe headaches. In some cases, patients also suffer from seizures as the cranial cavity becomes more constricted. The shafts of the long tubular bones increasingly widen.
Diagnosis and course of the disease
Diagnosis as early as possible and immediately subsequent therapy greatly improves the prognosis of patients with craniodiaphyseal dysplasia. The physician probably has an initial suspicion of hyperostosis by visual diagnosis. Imaging techniques are considered the most important diagnostic tool. For example, X-rays show extreme hyperostosis and sclerosis of all cranial bones. The clavicles or ribs may appear flared on imaging. The absent diaphyses on the long bones stand out clearly. A delineable, non-thickened cortical bone also fits into the clinical picture. Differentially, a distinction must be made from diseases such as Engelmann syndrome. Molecular genetic analyses are particularly useful for such a differential diagnosis.Engelmann syndrome shows alterations in the TGFB1 gene on mutation analysis, whereas craniodiaphyseal dysplasia affects the SOST gene.
Complications
Craniodiaphyseal dysplasia refers to a rare, genetic skeletal disorder. The symptom manifests directly on the facial skull by a severe proliferation of bone substance with accompanying sclerosis. Already in infancy, the genetic mutation is manifested by the shape of the skull and incorrectly positioned nasal passages, which can cause threatening respiratory problems. The resulting consequences of craniodiaphyseal dysplasia bring numerous life-limiting complications to the affected patient from infancy onwards. If timely clinical intervention is not made, the excess bone growth progresses. The interior of the skull narrows and the dentition does not form adequately. The thickening bone material constricts the auditory canal and there is a risk of hearing loss or even hearing loss. There is an increasing lack of space in the cranial cavity, and bone deposits invade the brain. Severe headaches, seizures, facial paralysis and epilepsies develop, as well as a reduction or regression of already mentally acquired abilities. Parents whose children are affected by craniodiaphyseal dysplasia should therefore seek early clinical intervention. After the imaging clarification, the differential diagnosis takes effect within the scope of the given possibilities. There is currently no basic therapy for craniodiaphyseal dysplasia. Attempts are being made to curb the uncontrolled progression of bone growth and its consequences. Various medications, as well as a calcium-reduced diet starting in infancy, help the affected individual to reduce the symptom.
When should you see a doctor?
Craniodiaphyseal dysplasia is often diagnosed immediately after birth. If this is the case, the doctor in charge will immediately inform the parents and then directly initiate treatment. In the case of less pronounced dysplasia, the diagnosis is made by the parents. A visit to the doctor is indicated if the newborn has problems breathing or suffers from watery eyes. External abnormalities such as the typical malformations of the face and teeth also indicate a disease that needs to be clarified and treated. Parents who notice signs of hearing loss or seizures in their child should consult a doctor. The same applies if the child complains of frequent headaches or gives the appearance of severe pain. During treatment, the child must be seen regularly by a doctor. This will ensure that recovery proceeds without complications. Because craniodiaphyseal dysplasia is associated with a range of symptoms, treatment may take months or even years. The general practitioner will consult other specialists for this purpose, always depending on what symptoms and complaints present themselves. Typically, neurologists, internists, otologists, surgeons, physical therapists and psychologists are involved in the treatment.
Treatment and therapy
Causal therapy does not yet exist for patients with craniodiaphyseal dysplasia. Such a therapy may be conceivable in the future through gene therapy approaches. At present, however, the disease can only be treated symptomatically. The goal of all therapeutic measures is above all to stop the excessive bone growth. Various steps can be taken to achieve this. For example, the progression of the disease can be stopped by medication. The drugs most commonly used are calcitriol and calcitonin. Since bone structure is dependent on calcium, a calcium-reduced diet can also make sense. This special diet should be applied in the long term and ideally should accompany the patient’s entire life. Medication with the artificial glucocorticoid prednisone has also shown positive effects. The earlier therapy is started, the more promising the outlook. Hyperostosis can be brought to a standstill in the first years of life if treated extremely early. In this way, the subsequent symptoms are drastically reduced. Under certain circumstances, surgical corrections can also be made as part of the therapy. Before the course of the disease has been brought under control, however, such corrections usually make little sense.
Outlook and prognosis
In congenital but very rare craniodiaphyseal dysplasia, there is a genetic mutation that cannot be repaired. Therefore, the prognosis for affected individuals is not too good. Doctors can only try to treat the symptoms and sequelae of the increasing bone growth in the head area. Therapy can only delay the progression of the disease. The proliferation of bone substance progresses inexorably in craniodiaphyseal dysplasia. Since current therapeutic options cannot reverse the underlying mutation at the embryonic stage, further generations of affected individuals will suffer. A striking feature of craniodiaphyseal dysplasia is a familial clustering. The manifestations associated with craniodiaphyseal dysplasia can already be observed in infants. Since all bone adhesions occur in the cranial region, they also affect the upper respiratory tract as well as hearing or vision. In addition, the interior of the skull is also increasingly affected by bone formation. This limits the therapeutic approaches for the subsequent complaints. The earlier the diagnosis can be made, the better the long-term prognosis. The increasing bone growth is inhibited by a low-calcium diet. In addition, appropriate medications as well as prednisone can be administered in infancy. An interdisciplinary treatment strategy achieves the best results. Surgical intervention makes sense for craniodiaphyseal dysplasia only when disease progression has been successfully contained.
Prevention
Prevention measures for craniodiaphyseal dysplasia do not yet exist. The disease is a genetic disorder associated with a familial predisposition. Therefore, only molecular genetic counseling can be used as a preventive measure.
Follow-up
In this disease, very few aftercare measures are available to the affected person in most cases. In some cases, this may even be completely limited, so that the affected person is dependent on a purely symptomatic treatment of the disease. Self-cure is not possible, as this is a genetically determined disease. Therefore, if the affected person wishes to have children, he or she should have a genetic examination and counseling to ensure that the disease does not recur in the children. The treatment itself is usually carried out with the help of various medications that can permanently alleviate and limit the symptoms. It is always important to ensure that the medication is taken regularly, and the correct dosage must be observed. In the case of children, it is above all the parents who should check that they are taking and using the medication correctly. Regular check-ups by a doctor are also necessary in order to permanently monitor the condition. Most malformations can be corrected by surgical intervention. Many of those affected are also dependent on psychological support from their own family in their daily lives, which has a positive effect on the further course of the disease. As a rule, this disease does not reduce the patient’s life expectancy.
What you can do yourself
In the case of craniodiaphyseal dysplasia, the affected patient has only limited effective measures at his disposal to positively influence the course of the disease. First and foremost is appropriate therapy for craniodiaphyseal dysplasia by a team of medical specialists. The disease begins to manifest itself in infancy, so that initially it is primarily the parents who contribute to the quality of life of the affected children. If the child is hospitalized, it often makes sense for the parents to be present in the hospital, thus providing the child with emotional support. In the course of the disease, there are often disturbances in the development of the teeth, so that the patients are often dependent on orthodontic therapy. This also requires the patient’s own cooperation in terms of wearing braces. In addition, there is evidence that a low-calcium diet curbs the progression of craniodiaphyseal dysplasia. Here, too, patients have considerable leeway with regard to their cooperation and thus their quality of life.Due to the breathing problems, patients refrain from certain sports, but practice strengthening exercises trained with a physiotherapist, even at home, if allowed by a doctor. Children with craniodiaphyseal dysplasia receive appropriate education in special schools.
