Oto-spondylo-megaepiphyseal dysplasia is a mutational skeletal dysplasia. The main symptoms of the patients are defects in the bone and cartilage tissue as well as sensorineural hearing loss. Treatment is purely symptomatic and usually includes pain therapy.
What is oto-spondylo-megaepiphyseal dysplasia?
Skeletal dysplasias are congenital disorders of the bones or cartilage tissue and are also known as osteochondrodysplasias. A myriad of disorders fall into the group of skeletal dysplasia. One of them is oto-spondylo-megaepiphyseal dysplasia (OSMED), a congenital and hereditary tissue defect. See eshaoxing for Atrioventricular Septal Defect Definition and Meaning.
The disease is also known as dysplasia spondyloepiphysaria and already manifests itself in the neonatal period with symptoms such as sensorineural hearing loss and skeletal anomalies. The prevalence of the disease is reported to be less than 1 case in 1,000,000 people. This means that oto-spondylo-megaepiphyseal dysplasia is one of the rare hereditary diseases and can occur in a homozygous as well as in a heterozygous form.
The homozygous form of the disease is called Nance-Sweeney syndrome, Insley-Astley syndrome, OSMED (autosomal recessive) or OSMED (homozygous). The terms OSMED (autosomal dominant), OSMED (heterozygous) and Pierre Robin syndrome with fetal chondrodysplasia, Stickler syndrome type III and Weissenbacher-Zweymüller syndrome (WZS) stand for the heterozygous form. To date, only about 30 cases of oto-spondylo-megaepiphyseal dysplasia have been reported in the literature.
Oto-spondylo-megaepiphyseal dysplasia is caused by mutations in the COL11A2 gene. The cause of the disease lies in the genes. The causative mutations are in the gene locus 6p21.32 or affect the COL2A1 gene in locus 12q13.11. Accordingly, in the context of the disease, it is precisely the genetic material that is involved in the formation of cartilage collagen that mutates.
The genes mentioned code for a protein that plays a crucial role in the formation of type XI collagen. Mutations in the genes lead to defects in the structure of the protein, which are associated with a loss of function. Because of this loss of function, no physiologically healthy type XI collagen can be produced in the patient’s body. For this reason, oto-spondylo-megaepiphyseal dysplasia is one of the type XI collagenopathies.
A majority of the cases documented to date are based on homozygous mutations in the COL11A2 gene at locus 6p21.3, which specifically encodes the alpha-2 chain of type XI collagen. Depending on the form, the disease is passed on in either an autosomal dominant or autosomal recessive mode of inheritance. Clinically, dysplasia has a significant overlap with other syndromes that are based on a mutation of the gene described.
Symptoms, Ailments & Signs
Patients with oto-spondylo-megaepiphyseal dysplasia suffer from a variety of symptoms, most of which involve cartilage and bone tissue. The main symptom of those affected is usually a sensorineural hearing loss. In addition, there are usually bone abnormalities such as enlarged epiphyses.
Skeletal dysplasia occurs with disproportionately shortened extremities. In addition to vertebral body anomalies, characteristic facial features often appear. In addition to an underdeveloped midface, typical fascial features are a conspicuously short nose with an anteverted nares, a flat nasal bridge and a long philtrum. In many cases, cleft palate, microgenia or hypertelorism also catch the eye.
The disease usually manifests itself in the second decade of life in the form of joint pain, which often results in limited mobility. This primarily affects the metacarpo-phalangeal joints, with osteoarthritis occurring in many cases at the same time as these symptoms. Sensorineural hearing loss is usually non-progressive. In individual cases, other symptoms can occur, which often overlap with other syndromes.
Diagnosis & course of disease
The diagnosis of oto-spondylo-megaepiphyseal dysplasia is based on clinical features. The first suspicion usually arises from visual diagnostics. Visual diagnosis is supported by typical X-ray findings such as shortened long bones to large epiphyses, enlarged metaphyses and coronary cleft vertebrae or platyspondylia.
Clinically, OSMED often overlaps with Weissenbacher-Zweymuller syndrome (WZS) or Stickler syndrome. The differential diagnostic differentiation from Stickler syndrome is based on the absence of ocular symptoms. A differential diagnosis between OSMED and WZS turns out to be difficult, since WZS is also based on heterozygous COL11A2 mutations. The prognosis for patients with oto-spondylo-megaepiphyseal dysplasia depends on the clinical symptoms in the individual case, especially on the severity of the osteoarthritis.
In this disease, sufferers suffer from various bone and joint problems. In most cases, this leads to pain, which can occur especially with exertion or movement. However, in many cases there is also pain at rest, which can lead to sleep disorders at night and thus also to depression or irritability in the person concerned.
The quality of life of the patient is thus significantly reduced due to the illness. Due to the permanent pain, the mobility of the affected person is usually restricted. In many cases, this delays the development or growth of the child, so that various symptoms can also occur in the patient in adulthood. The patients also suffer from hearing loss.
This cannot be treated causally and is therefore not curable. However, this can be counteracted with the help of a hearing aid. The treatment itself depends on the symptoms and is usually not associated with complications. The life expectancy of the patient is also not reduced in most cases.
When should you go to the doctor?
If hearing impairments occur or if the person concerned complains of irregularities in the area of the ears, a doctor should be consulted. Since it is a genetic disease, the first symptoms are documented in childhood. Decreased hearing ability is a characteristic feature of oto-spondylo-megaepiphyseal dysplasia. In everyday life, those affected usually only react to very loud noises, since most frequencies cannot be perceived and processed due to the sensorineural hearing loss.
Therefore, a doctor should be consulted as soon as the affected person can hear the environmental noises in a lower form in direct comparison to his fellow human beings. In addition, increased vigilance is required, since warning or danger signals are often not registered. All regions in the body where cartilage is located can be affected by the disease. If there are disturbances in the movement sequences or restrictions in the possibilities of movement, a doctor’s visit is necessary.
Pain in the joints, optical features in the face and unsteady gait must be presented to a doctor. Sleep disorders, rest pain, behavioral problems and a reduced sense of well-being are signs of an existing disease. There is a need for action so that adequate medical care is initiated to reduce the symptoms. Depressed mood, moodiness, or listlessness should be discussed with a doctor. If symptoms increase, a doctor should be consulted as soon as possible.
Treatment & Therapy
A causal treatment is not yet available for patients with oto-spondylo-megaepiphyseal dysplasia. Since it is a genetic defect, advances in the field of gene therapy could open up causal therapeutic pathways in the coming decades. However, gene therapy approaches have not yet reached the clinical phase.
For this reason, oto-spondylo-megaepiphyseal dysplasia is treated purely symptomatically. Not all symptoms of the disease are easily treatable. However, the fascial abnormalities can often be corrected by invasive procedures. In one operation, for example, a closure of the cleft palate can be achieved.
In addition, measures can be taken against moderate sensorineural hearing loss. In this context, audiometry including the fitting of a hearing aid is indicated. If no improvement in the hearing loss can be achieved despite these measures, the patients receive supportive therapy and learn sign language, for example.
In order to improve the quality of life of those affected, any joint pain is relieved. Conservative drug treatments are usually used for this. The sporadic administration of painkillers is often not enough to permanently stop the chronic pain. For this reason, a pump with painkilling substances can be implanted in those affected as part of pain therapy, for example.
Outlook & Forecast
As with many other hereditary diseases, the numerous side effects of oto-spondylo-megaepiphyseal dysplasia can hardly be alleviated. The fatal combination of skeletal dysplasia with sensorineural or sensorineural hearing loss, conspicuous spinal anomalies or skeletal damage, and enlarged epiphyses occurs very rarely. In addition, those affected have disproportionate and shortened limbs and a typical face shape.
To date, only about 30 people with oto-spondylo-megaepiphyseal dysplasia have been identified worldwide. This suggests that the severity of this malformation combination mostly leads to an abortion. The prospects of an improvement in the numerous complaints are not particularly good for those affected. The treating physicians can only surgically correct some of the malformations in the skeleton. They can also treat the sequelae of disorders caused by oto-spondylo-megaepiphyseal dysplasia.
For example, hearing impairments can be improved by fitting a hearing aid for sensorineural hearing loss. Cleft palate can be surgically closed. Pain in the spine or skeleton can be treated with physiotherapy or with painkillers. The possible degree of individual improvement depends on the severity of the congenital malformations and disorders. Because of the associated osteoarthritis, early joint replacement is often necessary. It is possible that this disease is one of the complex clinical pictures that can be prevented in later generations through genetic research.
To date, oto-spondylo-megaepiphyseal dysplasia can only be prevented to a limited extent. Since it is a hereditary disease, prevention focuses mainly on genetic counseling in the family planning phase.
Since oto-spondylo-megaepiphyseal dysplasia is a genetic disease, there are no direct treatment options. Only the symptoms that occur, such as hearing loss in the inner ear (sensorineural hearing loss), skeletal anomalies with vertebral body anomalies such as platyspondylia and cleft vertebrae and cleft palate can be treated accordingly and then require adequate follow-up treatment.
Closure of the cleft palate begins in infancy. However, outpatient follow-up care extends into adulthood, since regular check-ups should be carried out with the assessment of several specialist disciplines such as orthodontists, dentists, ENT specialists and speech therapists. At the age of about ten to twelve years, the jaw plate is often expanded again, this is often decided individually and depends on the severity of the clinical picture. Aesthetic corrections can also continue to be made in adulthood.
Due to the sensorineural hearing loss, so-called cochlear implants can already be implanted in infancy. Careful postoperative care and a precise, ongoing assessment of language development are required here. Another serious symptom is the onset of osteoarthritis with severe pain and restricted mobility.
Since drug therapy usually includes glucocorticoids and non-steroidal anti-inflammatory drugs, regular and close laboratory blood tests are indicated to prevent any organ damage that may occur as a side effect. Physiotherapeutic and osteopathic aftercare treatments to prevent further movement restrictions are also indicated.
You can do that yourself
Oto-spondylo-megaepiphyseal dysplasia often affects hearing, which has a disruptive effect on everyday life. In addition, the defective tissue in bones and cartilage can cause pain. To reduce this pain, there are suitable medications. It is also very important to follow the pain therapy recommendations.
Regular exercise therapy can reduce the painful consequences somewhat. Physiotherapy can also help against the symptoms and also against osteoarthritis and similar diseases. With everyday movements, however, it is important to assess the load correctly so that it does not hurt too much. If the joint and bone problems also lead to night pains, you may have trouble sleeping and side effects such as irritability and depression. As a result, the overall quality of life deteriorates. This is an important aspect, especially for younger patients.
Strict compliance with the medical instructions and gentle occupational therapy are effective methods of raising the spirits. There is no specific therapy for the hearing loss associated with this rare disease. Here, above all, increased attention is required in everyday life in order not to put yourself in danger. Furthermore, there is of course the option of wearing a hearing aid in order to participate as intensively as possible in life.