The clinical term multiple epiphyseal dysplasia is used in medicine to describe abnormalities at the joint ends of the long tubular bones. Mutations in protein-coding genes appear to be responsible for the abnormalities. Therapy focuses on aligning each affected joint surface.
What is multiple epiphyseal dysplasia?
Epiphyseal diseases are diseases of the joint ends of long long bones. In the heterogeneous disease group of epiphyseal displasias, these joint ends exhibit abnormalities. Growth disorders cause the abnormal growth of the epiphyses. The phenomenon is also called Fairbank disease or Ribbing-Müller disease. The disease belongs to the secondary growth disorders and is a consequence of chromosomal mutations in different expressions. The epiphyses of the hips and ankles are particularly affected. The prevalence of the disease is 1:20,000. Of the heterogeneous group of diseases, EDM1 has been the best studied to date. This subtype is inherited in an autosomal-dominant manner. However, autosomal recessive inheritance is also conceivable within the group of epiphyseal dysplasias. One of several special forms from this group of diseases is Meyer dysplasia of the femoral epiphyses. The disease group has not been conclusively investigated to date.
Causes
The cause of multiple epiphyseal dysplasias lies in the genetic material. Mutations of various genes trigger the growth disorders. For EDM1, mutations of the COMP gene have been documented as the cause. This gene codes for the oligomeric cartilage matrix protein. Due to the mutation, the structure of the protein is abnormal. Its functionality suffers and the structure of the bone matrix is disturbed. All other EMD types are documented in less detail as to their cause. The mutations appear to be in the genes COL9A2 at gene locus 1p33-p32.2, COL9A3 at gene locus 20q13.3, MATN3 at locus 2p24-p23, and COL9A1 at locus 6q13. Thus, in all forms, mutations of the proteins encoding the extracellular cartilage matrix are present. The latter mutation is a collagen IX abnormality. A final and more atypical form of EDM is associated with mutations in the SLC26A2 gene at gene locus 5q32-q33.1. Autosmal dominant inheritance is standard. Autosomal recessive forms are less common. Much of the etiopathogenesis remains unclear. Speculation is that the transport of protein moieties of proteoglycans is impaired. Thus, the protein moieties are unable to migrate from the rough endoplasmic reticulum to the Golgi apparatus.
Symptoms, complaints, and signs
Multiple epiphyseal dysplasia can be expressed at various stages of life. In early childhood, most patients are still asymptomatic. The first signs of epiphyseal disease are arthritic joint pain. The prearthrotic changes in multiple joints cause limitation of movement over time. Gait disturbances such as waddling gait are a characteristic sign of the disease. Moderate short stature may be equally characteristic. Depending on the actual cause, multiple epiphyseal lesions present in combination with additional symptoms. For example, multiple epiphyseal dysplasia is now associated with myopia. Hearing loss and facial dysmorphia are equally often associated with the heterogeneous group of diseases. Dysplasias primarily affect the hip and ankle joints. Pain radiates from the joints arthritically throughout the body.
Diagnosis and course of the disease
Diagnosis of multiple epiphyseal dysplasia depends on recognition of the signs on radiograph. The history prompts the physician to perform radiographic imaging. X-rays reveal symmetrical-looking changes in the epiphyses of various long bones. The epiphyseal nuclei appear delayed, are small, and fragment. Major and minor nuclei fuse to form abnormal joint ends. This fusion causes growth disturbances and deviations of the axes, thus causing the arthritic changes. Molecular genetic analysis can provide evidence of the gene mutations. The course of multiple epiphyseal dysplasia depends on the causative mutation, timing of diagnosis, and treatability. Early diagnosis has a favorable effect on prognosis.
Complications
Various malformations and abnormalities usually occur in this disease, mainly in the patient’s joints.This results in considerable restrictions in everyday life, and the patient’s movement may also be restricted. It is not uncommon for those affected to also suffer from severe joint pain, which can lead to sleep problems, especially at night. As a result, sufferers become irritable and the quality of life decreases significantly. Likewise, the pain from the joints can also radiate to other regions and cause discomfort there. In some cases, this disease also leads to short stature. Similarly, permanent pain can also cause psychological discomfort and depression. In some cases, certain activities in everyday life are not feasible for the affected person, so that he is dependent on the help of other people. It is not possible to treat the disease causally. However, many complaints and pains can be limited. However, the affected person is dependent on various therapies. As a rule, life expectancy is not limited. In some cases, surgical interventions can be used to alleviate the patient’s discomfort. In most cases, no particular complications occur.
When should one go to the doctor?
Joint discomfort and irregularities indicate health impairment. If they persist or increase in intensity, a doctor is needed. If the irregularities occur after physical overexertion or intense athletic activity, cooling the joints and adequate rest are often sufficient. If spontaneous healing occurs immediately after a restful night’s sleep, a doctor’s visit is not required. In the future, overexertion should be avoided and footwear should be checked for tolerance and optimized if necessary. If mobility or joint activity is restricted, a check-up with a doctor is advisable. Disturbances in locomotion, malpositions or a crooked posture must be discussed with a doctor to avoid permanent damage. If there is a developmental disorder, short stature or bad posture, a doctor should be consulted. Disorders of general movement or a diminished ability to perform daily responsibilities should be discussed with a physician. Hearing loss is considered a concern. If there is a decrease in hearing, a doctor should be consulted immediately. Pain in the joints or unusual deformities of the face are other signs of a condition requiring treatment. In addition, taking a pain-relieving medication to avoid side effects should only be done in consultation with the treating physician.
Treatment and therapy
There is no causative therapy for patients with EDM. The genetic mutation cannot be cleared. Treatment is symptomatic. Creating joint surfaces that are as congruent as possible is the focus of therapy in multiple epiphyseal dysplasia. The arthritic pain decreases due to the congruency of the joint surfaces and the joint does not take further damage. Surgeries are the treatment of choice to create congruent joint surfaces. These orthopedic operations ideally take place in childhood. In this way, consequential damage such as arthrosis can be contained in the best possible way. The number of operations required depends on the individual case. To improve the patient’s quality of life, painkillers can be given for severe pain. Acute pain, for example, can be contained by peripherally acting analgesics. Ideally, patients should remain active. To achieve this, physical therapy is the step of choice. Older patients of multiple epiphyseal dysplasia often suffer from osteoarthritis despite countermeasures. The onset of this secondary wear disease can often only be delayed by the above-mentioned therapeutic measures. In the case of severe osteoarthritis in one or more joints, joint replacement may become necessary. If several joints are affected, the replacement operations take place as far apart as possible. Accompanying physiotherapy is indispensable, especially after such operations. Other patients in this disease group do not require joint replacement for the rest of their lives despite the deformities. It may be possible in the future to find a causal therapy for the disease. Medical research is currently looking at approaches such as gene therapy.
Outlook and prognosis
The cause of multiple epiphyseal dysplasia is found in a mutation of genetics. This must not be altered by the treating physician. Legal requirements prohibit physicians from altering human genetics. Therefore, the disease is considered incurable. Immediately after birth and in the further course, the patient shows various malformations, optical abnormalities or disorders of sensory perception. Although no recovery can be achieved, scientists are constantly developing new methods to achieve relief from the individually pronounced symptoms. For this reason, in some cases it is possible to achieve improvements in the overall situation by starting treatment at an early stage and using various treatment steps as well as surgical interventions. If surgery proceeds without further complications, significant progress in stabilizing health can often be documented. Overall results are improved if the patient also completes physiotherapeutic exercises and training sessions outside of treatment to support the musculoskeletal system. In addition, various precautions should be taken to reduce stress on the joints. This contributes significantly to optimizing well-being and prevents further secondary diseases. Nevertheless, the burden of the disease as well as the resulting circumstances in everyday life is very high overall and the risk of developing a mental disorder is increased.
Prevention
The etiology of multiple epiphyseal dysplasia has not been conclusively determined. Therefore, there are no preventive measures. However, early treatment helps prevent sequelae.
Follow-up
Multiple epiphyseal dysplasia is a genetically caused disease that has no cure. For this reason, follow-up care for this disease does not refer to measures taken after complete recovery, but only to individual steps taken during therapy. Since complete recovery is not possible, only the symptoms of the disease can be treated. The early onset of osteoarthritis, for example, can be at least partially mitigated by means of shoe inserts and other orthopedic aids. In addition, physiotherapeutic treatment usually has a beneficial effect on the condition of patients with multiple epiphyseal dysplasia. The same is true for joint pain associated with the disease. Follow-up care for this disease tends to involve monitoring of individual procedures, such as surgical interventions. In the advanced stages of osteoarthritis, surgical interventions may be considered, for example, the use of artificial joints. In such a case, follow-up care is similar to that for other postoperative situations. Intensive physiotherapy is essential to accustom the patient to the new joint. A diet plan developed by a professional nutritionist can have a beneficial effect on the condition of osteoarthritis, as can a generally healthy lifestyle with light exercise.
Here’s what you can do yourself
Because multiple epiphyseal dysplasia is based on a genetic mutation, causal therapy is not possible. Therefore, self-help options are also limited. However, measures can be applied to alleviate the symptoms. An important complement to medical therapy is the maintenance of physical activity. Patients can learn exercises that help relieve pain through physiotherapeutic support. In addition, other alternative options for pain management should be tried. These may include acupuncture, hypnosis or progressive muscle relaxation. Doctors and physiotherapists provide information about the individually appropriate treatment options. It is important to apply the respective accompanying measures continuously. This is the only way to achieve long-term physical and psychological success with these therapies. A structured daily routine helps to take time for exercises and relaxation. In addition to such applications, it is important to involve the social environment. A healthy social life can help maintain an active lifestyle. An intact social network is also important for support during acute pain and other severe symptoms of the disease. Despite a difficult prognosis and lengthy treatments, a positive contribution to maintaining quality of life can thus be made on an individual basis.
