Multiple cartilaginous exostoses are multiple and hereditary exostoses. An autosomal dominant inherited mutation underlies the benign bone tumors. Treatment consists largely of surgical ablation of the tumors.
What are multiple cartilaginous exostoses?
Exostoses involve a demarcated neoplasm of compact bone substance that is directed outward. Exostoses are hyperostoses, or hyperplasias, of bone tissue characterized by an increase in cell number. In most cases, an exostosis is a hyperplastic reaction. In this case, the bone changes in response to stimuli such as pressure. In still other cases, exostosis is a benign tumor disease associated with the formation of osteomas and characterized by slow growth. There are also hereditary exostoses. One associated disease is multiple hereditary exostosis, or MHE. This is an autosomal dominant inherited disorder with multiple benign bone tumors, also known as multiple cartilaginous exostoses. Although it is a congenital disorder, the tumors are usually not yet present at birth. Development usually begins in childhood or adolescence and corresponds to a slowly progressive development. The tumors are osteochondromas with hyaline cartilage. The incidence of the disease is reported to be one case in 50,000 people. With this frequency, the disease is one of the most common exostosis diseases, and women and men are equally affected.
Causes
Multiple hereditary exostoses are a hereditary disease for which familial clustering has been observed. Thus, a familial form is present in about 70 percent of all patients and is passed on in the autosomal dominant mode of inheritance. In only about 30 percent of cases does the disease occur sporadically. The causes of the phenomenon are to be found in genetics. In the majority of cases, hereditary mutations are present. In the sporadic proportion of those affected, the disease corresponds to a new mutation that is probably related to exogenous factors such as environmental toxins. The causative mutations for multiple hereditary exostoses have now been identified. They are mutations in the genes EXT1 and EXT2 on chromosome 8 and chromosome 11. These genes code for the proteins exostosin 1 and exostosin 2 in the DNA. The two proteins are so-called glycosyltransferases that modify heparan sulfate within the Golgi apparatus. Heparan sulfate is a proteoglycan involved in angiogenesis. Due to the mutations, the proteins to modify this substance are not properly assembled. How this mutation and loss-of-function enzymes are associated with bone tumor development remains unclear to date.
Symptoms, complaints, and signs
The clinical presentation of patients with multiple hereditary exostoses is highly variable. In many cases, the disease is asymptomatic. Clinically manifest cases are characterized by uncontrolled exostosis growth that occurs near the growth plate of bone ends and is encased in cartilage. The bones deform, producing uneven growth in length of the legs, arms, hands, feet, toes, or fingers. The multiple exostoses can promote limited mobility. Generalized short stature is also a possible consequence. Some patients complain of pain, usually associated with nerve compression. Clinically, different courses are distinguished for the disease. According to Pedrini, MHE is classified into three stages:
- In class 1, no deformities arise from the tumors and equally few functional limitations, since there are usually fewer than five exostoses.
- Class 2 multiple cartilaginous exostoses are associated with deformities but no functional limitations.
- Deformities with functional limitations characterize class 3
.
How many exostoses are present varies from case to case. Thus, the accompanying pain and impairment symptoms are also extremely variable.
Diagnosis and disease progression
The bone tumors of multiple cartilaginous exostosis are not present at birth, so the diagnosis is typically not made until 12 years of age. Because in many cases the exostoses do not result in pain or impairment, an even later diagnosis is conceivable.Diagnosis focuses on imaging techniques such as X-ray imaging, and a biopsy is usually taken to assess the tumors. Histological analysis proves the benign nature of the tumors. In case of doubt, molecular genetic analysis can take place to provide evidence of causative mutations. However, this analysis is sometimes very costly. The prognosis of patients depends on the severity of the disease in each individual case. In cases of severe exostosis, therapeutic results are often unsatisfactory.
Complications
In this disease, affected individuals suffer from very severe limitations in movement in most cases. Usually, there is also a short stature, which has a very negative effect on the quality of life of the patients. Furthermore, there may be restrictions in everyday life, so that the affected person is dependent on the help of other people in everyday life. Not infrequently, pain also occurs, which continues to interfere with everyday life. The affected person also suffers from sleep complaints and sleep disturbances if the pain also occurs at night in the form of pain at rest. In most cases, early diagnosis and treatment is not possible. However, since the tumors are usually benign, they do not pose a particular threat to health in the first place. For this reason, treatment usually only takes place if the disease leads to severe limitations or pain in everyday life. No particular complications occur and there is no reduction in life expectancy. However, in many cases, patients are dependent on physiotherapy.
When should you see a doctor?
Swelling or growths on the bones are uncommon. If they occur after a bruise or a fall, spontaneous healing can often occur. If the discomfort has disappeared after cooling or adequate night sleep, a doctor is usually not needed. If the irregularities persist or increase in intensity, a visit to the doctor should be made, as there is a condition requiring treatment. If there are disturbances in movement patterns, restrictions in general mobility or problems with joint activity, a doctor is needed. If pain occurs, there is an increased need for action. Independent use of pain medication is generally not recommended. Due to possible risks and side effects, medication should only be taken in consultation with the attending physician. Deformations of the bone structure, poor posture and muscle tension should be examined by a physician. If participation in social and societal life decreases due to the complaints, if everyday obligations can no longer be fulfilled or if accustomed sporting activities can no longer be performed, a doctor is needed. Inner restlessness, behavioral problems, changes in the appearance of the skin, and sleep disorders should be examined and treated. Emotional and mental stress, anxiety or severe weight changes are signs of a health impairment. The affected person needs medical help so that relief from the symptoms can occur.
Treatment and therapy
As long as multiple cartilaginous exostoses do not show symptoms, treatment of the patient is not mandatory. Causative treatment cannot occur anyway because the genetic mutation is irreversible. Thus, only symptomatic treatment options are available for patients with hereditary exostoses. These therapeutic approaches are usually only implemented when the exostoses impair the patient’s mobility and everyday life or when severe pain limits the patient’s quality of life. In such cases, the exostoses are removed invasively by surgery. The surgeon proceeds generously in this procedure. The more he removes, the less likely recurrences are to occur. If the exostoses promote secondary diseases such as osteoarthritis in old age, the use of prosthetic joints may become necessary. If there is extreme pain symptomatology, the patient’s quality of life may be improved with pain-relieving medications. In some cases, physical therapy takes place to combat movement limitations.
Outlook and prognosis
The prognosis for multiple cartilaginous exostoses varies.It depends on the growth propensity of the benign tumor and the individual symptoms. The disease usually accompanies patients throughout their lives. A progress control takes place regularly. This can be a psychological burden due to the incalculability of the onset of the disease. In the worst case, those affected suffer restrictions in their quality of life. Pain and movement difficulties characterize everyday life. Because of the possible malignant degeneration, multiple cartilaginous exostoses can also shorten life. Statistically, this occurs in five percent of all cases. The disease is diagnosed in about equal numbers in both sexes. Most patients are still children when diagnosed and are in their twelfth year. Multiple cartilaginous exostoses stop forming at the end of the physical growth phase. If they continue to grow in adulthood, this indicates a malignant degeneration and thus an unfavorable prognosis. In therapeutic practice, it appears problematic that multiple cartilaginous exostoses form recurrences. Therefore, surgical interventions often lead to unsatisfactory results. This is also due to the fact that more than twenty exostoses are found in many patients.
Prevention
Multiple cartilaginous exostoses are hereditary exostoses. For this reason, genetic counseling at the family planning stage is considered one of a few ways to prevent the condition. However, its occurrence is not completely ruled out even if a decision is made not to have children of one’s own, as new mutations could also lead to the disease.
Follow-up
When growth is complete, the development of new exostoses usually also ends, so the disease does not worsen from this point on. Even if all functional limitations have been eliminated through physical therapy and surgical procedures, regular checkups should continue. If an exostosis continues to increase in size or develops anew, this is an indication of degeneration, which necessitates renewed treatment. Some consequences of multiple cartilaginous exostoses accompany patients throughout their lives. Leg length discrepancies or axial deviations in the joints must be treated continuously with orthoses and physiotherapy to prevent secondary diseases such as osteoarthritis or other signs of wear and tear. In general, an active lifestyle with regular exercise is recommended. This maintains the mobility of restricted joints, sometimes even improving it somewhat. In the case of severe restrictions, sports that are easy on the joints, such as swimming or walking, are indicated. Strength training strengthens the musculature, which serves as a support for deformed joints and thus relieves them. The psychological consequences of multiple cartilaginous exostoses should also not be underestimated. Because they are different, children in particular often experience exclusion and bullying. Psychotherapy adapted to the symptoms or attendance of self-help groups can help to gain positive experiences.
What you can do yourself
Until the completion of puberty and the growth phase, surgical corrections are contraindicated, as they trigger even more bone growth and thus worsening. Nevertheless, to alleviate disease-related symptoms until this time, relatives have several options. Intensive physiotherapy and medical massages prove to be soothing even in the case of significant movement restrictions and can, under certain circumstances, make the symptoms disappear completely. The exercises applied can also be continued in the home environment. In order to achieve an improvement in the quality of life, the pain and the associated lack of sleep must be combated first and foremost. Mattress toppers and chair pads provide good cushioning and relieve pressure on the painful ganglions. Many sufferers also experience a significant worsening of their symptoms during the colder months of the year. Warming gel packs, hot water bottles or special heat-storing heating pads provide rapid relief. For smaller children, warm cuddly toys for the microwave have also proved effective. Electrically operated electric blankets are not advisable, as they carry the risk of overheating and can lead to fires in the home. Parents must ensure that children have access to prescribed painkillers at school if necessary. Ideally, these should be placed directly in the classroom.To avoid overdose, it helps to have a chart in which each intake is briefly documented.
