Oto-spondylo-megaepiphyseal dysplasia is a mutation-related skeletal dysplasia. Patients suffer lead symptomatically from defects of bone and cartilage tissue and sensorineural hearing loss. Treatment is purely symptomatic and usually includes pain management.
What is oto-spondylo-megaepiphyseal dysplasia?
Skeletal dysplasias are congenital disorders of bone or cartilage tissue and are also known as osteochondrodysplasias. A myriad of disorders fall into the skeletal dysplasia group. One of these is oto-spondylo-megaepiphyseal dysplasia (OSMED), a congenital and heritable tissue defect. The condition is also known as dysplasia spondyloepiphysaria and manifests in the neonatal period with symptoms such as sensorineural hearing loss and skeletal abnormalities. The prevalence of the disease is reported to be less than one case per 1 000 000 people. Thus, oto-spondylo-megaepiphyseal dysplasia is one of the rare inherited diseases and can occur in both a homozygous and a heterozygous form. The homozygous form of the disease is referred to as Nance-Sweeney syndrome, Insley-Astley syndrome, OSMED (autosomal recessive), or OSMED (homozygous). For the heterozygous form, the names are OSMED (autosomal dominant), OSMED (heterozygous), and Pierre-Robin syndrome with fetal chondrodysplasia, Stickler syndrome type III, and Weissenbacher-Zweymüller syndrome (WZS). To date, only about 30 cases of oto-spondylo-megaepiphyseal dysplasia have been reported in the literature.
Causes
Oto-spondylo-megaepiphyseal dysplasia is caused by mutations in the COL11A2 gene. Accordingly, the cause of the disease is in the genes. The causative mutations are located in gene locus 6p21.32 or affect the COL2A1 gene in locus 12q13.11. Consequently, in the context of the disease, exactly the gene material involved in the formation of cartilage collagen mutates. The mentioned genes code for a protein that specifically 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. Due to this loss of function, physiologically healthy type XI collagen cannot be produced in the patient’s body. For this reason, oto-spondylo-megaepiphyseal dysplasia is considered a type XI collagenopathy. 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 transmitted in either autosomal dominant or autosomal recessive inheritance. Clinically, dysplasia results in substantial overlap with other syndromes based on mutation of the described gene.
Symptoms, complaints, and signs
Patients with oto-spondylo-megaepiphyseal dysplasia suffer from a variety of symptoms, most of which involve cartilage and bone tissue. Leading symptomatically, affected individuals usually present with sensorineural hearing loss. In addition, bone abnormalities such as enlarged epiphyses are usually present. There are skeletal dysplasias with disproportionately shortened extremities. In addition to vertebral body anomalies, characteristic facial features often occur. Typical fascial features include an underdeveloped midface, a conspicuously short nose with anteverted nares, a flat nasal bridge, and a long philtrum. In addition, in many cases cleft palate, microgenia or hypertelorism are noticeable. In most cases, the disease manifests itself in the second decade of life in the form of joint pain, often resulting in limited mobility. This mainly affects the metacarpo-phalangeal joints, with osteoarthritis occurring simultaneously with these symptoms in many cases. Sensorineural hearing loss is usually non-progressive. In individual cases, other symptoms may occur, often overlapping with other syndromes.
Diagnosis and disease progression
Diagnosis of oto-spondylo-megaepiphyseal dysplasia is based on clinical features. The initial suspicion usually arises by gaze diagnosis. The visual diagnosis is supported by typical radiographic findings such as shortened long bones to large epiphyses, expanded metaphyses, and coronary cleft vertebrae or platyspondyly. OSMED overlaps clinically particularly frequently with Weissenbacher-Zweymuller syndrome (WZS) or Stickler syndrome.The differential diagnosis of Stickler syndrome is based on the absence of ocular symptoms. Differential differentiation between OSMED and WZS is difficult because WZS is also caused by heterozygous COL11A2 mutations. The prognosis for patients with oto-spondylo-megaepiphyseal dysplasia depends on the clinical symptoms in each individual case, such as, most importantly, the severity of osteoarthritis.
Complications
In this disease, affected individuals suffer from various bone complaints and joint pain. In most cases, this involves pain, which can occur primarily during exertion or movement. However, in many cases there is also pain at rest, which can lead to sleep problems at night and thus to depression or irritability on the part of the affected person. The patient’s quality of life is thus significantly reduced as a result of the disease. Due to the permanent pain, the mobility of the affected person is usually also restricted. In many cases, this delays the development or growth of the child, so that the patient may also suffer from various complaints in adulthood. Patients also suffer from hearing loss. This cannot be treated causally and is therefore not curable. However, it 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 patient’s life expectancy is also not reduced in most cases.
When should you see a doctor?
If hearing limitations occur or the affected person complains of irregularities in the ears, a doctor should be consulted. Because it is a genetic condition, the first symptoms are documented in childhood. Decreased hearing ability is a characteristic feature of oto-spondylo-megaepiphyseal dysplasia. Affected individuals usually only react to very loud sounds in everyday life, as most frequencies cannot be perceived and processed due to sensorineural hearing loss. Therefore, a doctor should be consulted as soon as the affected person can hear environmental sounds in a lower form in direct comparison to his or her fellow human beings. In addition, increased vigilance is required, as warning or danger signals are often not registered. All regions of the body in which cartilage is located can be affected by the disease. If there are disturbances of the movement processes as well as restrictions of the movement possibilities, a visit to the doctor is necessary. Pain of the joints, visual peculiarities of the face as well as gait unsteadiness should be presented to a doctor. Sleep disturbances, pain at rest, behavioral problems as well as a reduced sense of well-being are signs of an existing disease. Action is needed to ensure that adequate medical care is initiated to alleviate the symptoms. A depressed mood, moodiness or apathy should be discussed with a physician. If symptoms increase, a physician should be consulted as soon as possible.
Treatment and therapy
Causal treatment is not yet available for patients with oto-spondylo-megaepiphyseal dysplasia. Because it is a genetic defect, advances in gene therapy may open causal therapeutic avenues in the coming decades. However, to date, gene therapy approaches have not reached the clinical phase. For this reason, oto-spondylo-megaepiphyseal dysplasia is treated purely symptomatically. Not all symptoms of the disease are readily treatable. However, the fascial abnormalities can often be corrected by invasive procedures. In one operation, for example, closure of the cleft palate can be achieved. In addition, moderate sensorineural hearing loss can be addressed. In this context, audiometry including the fitting of a hearing aid is indicated. If no improvement in hearing loss can be achieved despite these measures, patients receive supportive therapy and learn sign language, for example. To improve the quality of life of those affected, any joint pain is alleviated. Conservative drug treatments are usually used for this purpose. The sporadic administration of painkillers is often not sufficient to permanently relieve the chronic pain.Therefore, as part of pain therapy, affected individuals can be implanted with, for example, a pump containing analgesic substances.
Outlook and prognosis
As with many other hereditary disorders, the numerous concomitant symptoms of oto-spondylo-megaepiphyseal dysplasia can hardly be alleviated. The fatal combination of skeletal dysplasia with sensorineural hearing loss or sensorineural hearing loss, striking spinal abnormalities or damage to the skeleton, and enlarged epiphyses occurs very rarely. In addition, affected individuals have disproportionate and shortened limbs and a typical facial shape. To date, only about 30 affected individuals with oto-spondylo-megaepiphyseal dysplasia have been reported worldwide. This suggests that the severity of this combination of malformations usually leads to abortion. The prospects for improvement of the numerous complaints are not particularly good for those affected. The treating physicians can only surgically correct some of the malformations on the skeleton. They can also treat the secondary symptoms of disorders caused by oto-spondylo-megaepiphyseal dysplasia. For example, hearing disorders can be improved by fitting a hearing aid for sensorineural hearing loss. Cleft palates can be closed surgically. Spinal or skeletal pain can be treated with physiotherapy or analgesic medications. The possible degree of individual improvement depends on the severity of the congenital malformations and disorders. Because of concomitant osteoarthritis, early joint replacement is often necessary. It is possible that this disease is one of the complex conditions that can be prevented in later generations through genetic research.
Prevention
To date, prevention of oto-spondylo-megaepiphyseal dysplasia is limited. Because it is a hereditary condition, prevention has focused primarily on genetic counseling during the family planning phase.
Follow-up
Because oto-spondylo-megaepiphyseal dysplasia is a genetic disorder, there are no direct treatment options. Only the presenting symptoms such as sensorineural hearing loss (sensorineural hearing loss), skeletal abnormalities with vertebral body anomalies such as platyspondyly and cleft vertebrae, and cleft palate can be treated appropriately and then require adequate follow-up treatment. Closure of cleft palate begins in infancy. However, outpatient follow-up care continues into adulthood, as regular check-ups should be carried out with the involvement of several specialist disciplines such as orthodontists, dentists, ENT specialists and speech therapists. At the age of about ten to twelve years, bone augmentation of the jaw plate often takes place 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 inner ear hearing loss, so-called cochlear implants can already be implanted in infancy. In this case, careful post-operative care and precise, ongoing assessment of speech development are required. Another serious symptom is the onset of osteoarthritis with severe pain and limitation of movement. Because drug therapy usually includes glucocorticoids and nonsteroidal anti-inflammatory drugs, regular and close laboratory chemistry blood monitoring is indicated to prevent any organ damage that may develop as a side effect. Physical therapy and osteopathic follow-up treatments to prevent further movement restrictions are also indicated.
Here’s what you can do yourself
Oto-spondylo-megaepiphyseal dysplasia often impairs hearing, which is disruptive in everyday life. In addition, pain can occur due to the defective tissue on the bones and cartilage. Appropriate medications are available to reduce this pain. Following pain therapy recommendations is also very important. Regular exercise therapy can reduce the painful consequences somewhat. In addition, physiotherapy can help against the discomfort and also against osteoarthritis and similar diseases. However, with everyday movements, it is important to assess the load correctly so that it does not hurt too much.If the joint and bone complaints also lead to pain at night, sleep disorders and secondary symptoms such as irritability and depression may occur. As a result, the overall quality of life deteriorates. This is an important aspect, especially for younger patients. Close adherence to the doctor’s instructions and gentle occupational therapy are effective methods to lift the mood. There is no specific therapy for the hearing loss associated with this rare disease. Here, above all, increased attention in everyday life is necessary in order not to put oneself in danger. Furthermore, there is of course the possibility of wearing a hearing aid to participate as intensively as possible in life.
