CD stands for Craniodiaphyseal dysplasia. Craniodiaphyseal dysplasia is a congenital skeletal disorder associated with hyperostosis and sclerosis of the facial skeleton. The cause is a genetic mutation of the bone structure-inhibiting genes. Therapy is symptomatic and focuses on stopping the progression of the disease.
What is Craniodiaphyseal Dysplasia?
In a large number of cases, craniodiaphyseal dysplasia does not occur sporadically but tends to run in families. Both autosomal recessive and autosomal dominant inheritance have been identified as inheritance for the disease. See AbbreviationFinder for abbreviations related to CD.
In the case of hyperostosis, the bone substance increases abnormally. Hyperostosis of the skull is a group of diseases associated with such an increase in bone substance in the region of the skull. Craniodiaphyseal dysplasia is characterized by congenital hyperostosis of the skull and is one of the skeletal disorders.
The Australian doctor John Halliday first described the disease in the mid-20th century. Frequency is given with a prevalence of less than 1 case in 1,000,000 people. This makes the skeletal disorder an extremely rare cranial dysplasia.
The complex of hyperostosis and stenosis of the facial and cranial bones has now been traced back to a genetic cause. Due to the few documented cases so far, not all the connections between the disease have been finally clarified. For this reason, the therapy options are currently limited.
In a large number of cases, craniodiaphyseal dysplasia does not occur sporadically but tends to run in families. Both autosomal recessive and autosomal dominant inheritance have been identified as inheritance for the disease. In the autosomal dominant form, the disease is based on a new mutation in the SOST gene. The gene is located at location 17q21.31 and is considered one of the most important inhibitors for bone formation.
The mutation of the SOST genes is responsible for a variety of hereditary bone diseases, such as VDB. In the case of a mutation, the gene can no longer fulfill its inhibiting tasks and the bone structure becomes excessive. This fundamentally distinguishes the hyperostosis of craniodiaphyseal dysplasia from other types of hyperostosis.
Most of these diseases are based on a functional disorder of the osteoclasts or osteoblasts. The genetic disposition is considered to be proven in connection with the disease. Which other factors play a role in the outbreak of the disease has not been conclusively clarified.
Symptoms, Ailments & Signs
The clinical picture of craniodiaphyseal dysplasia is characterized by various clinical criteria that already manifest themselves in infancy. Affected infants usually have severely blocked 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.
In addition, the tear ducts of the patients are often obstructed after this phenomenon. In the course of the disease, progressively growing nasal protuberances made of bony substance form on the lower jaw of most of those affected. Hyperostosis of the facial skeleton progresses and develops into leontiasis ossea. In most cases, the tooth development of the patients is disturbed or delayed. The interior of the skull narrows as the disease progresses.
The narrowing also affects the foramina and causes consecutive optic atrophy. Symptoms such as hearing loss and more or less severe headaches can accompany this. In some cases, the patients also suffer from seizures as the space inside the skull increases. The shafts of the long tubular bones widen progressively.
Diagnosis & course of disease
Diagnosis as early as possible and subsequent therapy improves the prognosis of patients with craniodiaphyseal dysplasia significantly. The doctor probably already harbors a first suspicion of hyperostosis through visual diagnosis. Imaging methods are the most important diagnostic tool. For example, x-rays show extreme hyperostosis and sclerosis of all skull bones.
The clavicles or ribs may appear dilated on imaging. The missing diaphyses on the long bones are clearly visible. A definable, non-thickened cortex also fits into the clinical picture. In terms of differential diagnosis, it must be differentiated from diseases such as Engelmann syndrome. Molecular genetic analyzes are particularly suitable for such a differential diagnosis. Engelmann syndrome shows changes in the TGFB1 gene on mutational analysis, while craniodiaphyseal dysplasia affects the SOST gene.
Craniodiaphyseal dysplasia is a rare, genetically determined skeletal disease. The symptom manifests itself directly on the facial skull through a strong increase in bone substance with accompanying sclerosis. The genetic mutation can already be seen in infancy by the shape of the skull and incorrectly created nasal passages, which can cause dangerous breathing problems.
The resulting consequences of craniodiaphyseal dysplasia bring numerous life-limiting complications to the affected patient from infancy. If clinical intervention is not timely, the excessive bone growth progresses. The interior of the skull narrows and the rows of teeth do not develop adequately. The thickening bone material narrows the auditory canal and there is a risk of hearing loss.
There is an increasing lack of space in the cranial space, and bone deposits penetrate into the brain. Severe headaches, seizures, facial paralysis and epilepsies occur, as well as underdevelopment or regression of the mental abilities already acquired. Parents whose children are affected by craniodiaphyseal dysplasia should therefore seek clinical measures at an early stage.
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. Efforts are being made to curb the uncontrolled progression of bone growth and its consequences. Various medications and a low-calcium diet from infancy help those affected to reduce the symptoms.
When should you go to the doctor?
Craniodiaphyseal dysplasia is often diagnosed immediately after birth. If this is the case, the responsible doctor will inform the parents immediately and then initiate treatment directly. In the case of less severe dysplasia, the diagnosis is made by the parents. A doctor’s visit is indicated if the newborn has trouble breathing or suffers from watery eyes. External abnormalities such as the typical malformations on 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 see a doctor. The same applies if the child frequently complains of headaches or gives the appearance of severe pain. During treatment, the child must be regularly presented to a doctor. This ensures that recovery proceeds without complications. Since craniodiaphyseal dysplasia is associated with a number of symptoms, therapy can take months or even years. The general practitioner will consult other specialists for this purpose, always depending on which symptoms and complaints appear. Typically neurologists, internists, ear specialists, surgeons, physical therapistsand psychologists involved in treatment.
Treatment & Therapy
A 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 the present time, however, the disease can only be treated symptomatically. The aim of all therapeutic measures is above all to stop excessive bone growth. There are various steps to do this.
The progression of the disease can be stopped with medication, for example. Calcitriol and calcitonin are the most commonly used medicationsused. Since the bone structure is dependent on calcium, a calcium-reducednourishmentmake sense. This special diet should be applied over the long term and should ideally accompany the entire life of the patient.
Drug treatment of patients with the artificial glucocorticoid prednisone has also shown positive effects. The earlier therapy is started, the more promising the prospect. If treated extremely early, hyperostosis can be brought to a standstill in the first few years of life. In this way, the subsequent symptoms are drastically reduced.
Under certain circumstances, surgical corrections can also be made as part of the therapy. Such corrections usually make little sense until the course of the disease has been brought under control.
Outlook & Forecast
Craniodiaphyseal dysplasia, which is congenital but very rare, is caused by an irreparable genetic mutation. Therefore, the prognosis for those affected is not very good. The doctors can only try to treat the symptoms and consequences of the increasing bone growth in the head area. Therapy can only delay the course of the disease. In craniodiaphyseal dysplasia, the proliferation of bone substance progresses inexorably.
Since today’s therapy options cannot reverse the underlying mutation in the embryo stage, further generations of those affected will suffer from it. Familial accumulation of craniodiaphyseal dysplasia is striking. The symptoms associated with craniodiaphyseal dysplasia can already be seen in infants. Since all bone adhesions take place in the skull area, the upper respiratory tract as well as hearing or vision are also affected.
In addition, the interior of the skull is 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 medication and prednisone can be administered even in infancy.
An interdisciplinary treatment strategy achieves the best results. Surgical intervention in craniodiaphyseal dysplasia only makes sense if the progression of the disease has been successfully contained.
Preventive measures for craniodiaphyseal dysplasia do not yet exist. The disease is a genetic disease associated with a familial disposition. Therefore, only molecular genetic counseling can be used as a kind of preventive measure.
In most cases, those affected with this disease have very few follow-up measures available. In some cases, this can even be completely limited, so that the person concerned is dependent on purely symptomatic treatment of the disease. Self-healing cannot occur because it is a genetic disease.
Therefore, if the person concerned wants to have children, they should have a genetic examination and counseling carried out so 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 relieve and limit the symptoms. It is always important to ensure that it is taken regularly, and the correct dosage must also be observed.
In the case of children, it is primarily the parents who should monitor the correct intake and application. Regular check-ups by a doctor are also necessary to permanently check the condition of the disease. Most malformations can be corrected by surgical intervention. Many of those affected are also dependent on psychological support from their own families in their everyday 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.
You can do that yourself
In the case of craniodiaphyseal dysplasia, the affected patient has only limited effective measures available that positively influence the course of the disease. The first priority is appropriate therapy for craniodiaphyseal dysplasia by a team of specialists. The disease begins to manifest itself in infancy, so that it is primarily the parents who contribute to the quality of life of the affected children. When children are hospitalized, it often makes sense for the parents to be present in the hospital so that the child can receive 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. Your own cooperation is also required when it comes to wearing braces. There is also evidence that a low-calcium diet slows the progression of craniodiaphyseal dysplasia. Here, too, the patients have considerable leeway in terms of their cooperation and thus their quality of life.
Due to the breathing problems, the patients do without certain types of sport, but also practice strengthening exercises trained with a physiotherapist at home if this is medically permitted. Children with craniodiaphyseal dysplasia receive an adequate education in special schools.