What Is Hereditary Multiple Osteochondromas?

Overview

Hereditary Multiple Osteochondromas (HMO), also known as Multiple Hereditary Exostoses (MHE), is a rare genetic disorder characterised by the development of multiple benign bone tumours called osteochondromas. Osteochondromas are bony lumps (Fig 1) that typically appear during childhood or adolescence near the growth plates of parts of the skeletal system, including long bones, ribs and vertebrae.1 These bony spurts grow outward from the end of the bony elements but, more commonly, the end of long bones, also known as the metaphysis.  Osteochondromas are often associated with a reduction in skeletal growth, bony deformities and problems with one’s nerves. The median age of diagnosis is three years, and nearly all affected individuals are diagnosed by the age of 12. The risk for malignant degeneration to osteochondrosarcoma (bone cancer) increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%).2 HMO is primarily caused by mutations in the EXT1 or EXT2 genes, which are responsible for producing proteins involved in bone growth and development.3 The condition is autosomal dominant, meaning that a child has a 50% chance of inheriting the mutated gene from an affected parent. Diagnosis of HMO involves a combination of clinical evaluation, including genetic testing, to identify mutations in the mutated genes.⁴ Management and treatment of HMO aim to minimise symptoms, prevent complications, and improve quality of life.⁵ This article aims to provide an overview of the causes, signs and symptoms, diagnosis, management, and treatment options for HMO.

Fig 1: X-ray image showing annotations of bony spurts of ostechondrosarcoma.¹¹

Causes

As previously stated, HMO is primarily caused by mutations in the EXT1 or EXT2 genes, which are responsible for producing certain enzymes involved in bone development and growth regulation. These mutations disrupt the normal production and regulation of a protein called heparan sulphate, leading to the formation of osteochondromas. Some studies have suggested that the EXT1 and EXT2 genes may function as tumour suppressors, hence why mutations in these genes lead to the formation of osteochondromas.6 These mutations are usually inherited in an autosomal dominant pattern, meaning that only a single copy of the affected gene has to be present for an individual to inherit the particular disease. Further, autosomal dominance means that the affected individual has a 50% chance of passing the condition to each of their children. Usually, the abnormal gene is inherited from either parent; however, there are cases where individuals have acquired the disease as a result of a new mutation with no family history of HMO.

Signs and symptoms

The signs and symptoms of HMO vary between individuals and the location of the disease in the body. However, below are some of the most commonly reported symptoms:⁶

• Skeletal deformities (bowed arms and legs)
• Unequal limb lengths
• Shortened stature
• Restricted joint movement
• Nerve compression leads to symptoms like tingling, numbness, or weakness
• urinary problems

Diagnosis

Most HMOs can be asymptomatic (without symptoms) and found incidentally on imaging; however, for those experiencing symptoms, the diagnosis of HMOs can be established in a number of ways, including clinical examination, imaging or genetic testing.

Clinical Examination: A thorough history confirming similar symptoms in the family or a family history of HMO can help in confirming the diagnosis. A thorough physical examination can help identify the presence of multiple osteochondromas, assess skeletal abnormalities, and evaluate functional limitations.⁷

Imaging: characteristic radiographic findings of multiple osteochondromas on X-rays, CT scans or MRI scans. Typical radiography findings are cartilage-capped bony growths on growth plates of bones. The scans are commonly used to visualise osteochondromas, determine their size and location, and evaluate their impact on surrounding tissues.²

Genetic testing, sometimes called genomic testing, finds changes, such as mutations or variants in an individual DNA, which may lead to health problems. Genetic tests are done using a blood or spit sample, and results are usually ready in a few weeks. A pathogenic variant identified in the EXT1 or EXT2 genes on molecular genetic testing provides a definitive diagnosis of HMO.⁸

Management and treatment

The management of HMO is primarily focused on symptom relief, regular monitoring and prevention of complications, improving quality of life and psychological support for affected individuals and their families.⁵
Treatment options may include:

• Regular Monitoring: Routine imaging and clinical evaluations are essential to monitor the growth and progression of osteochondromas, detect potential complications, and guide treatment decisions.
• Orthopaedic Interventions: Surgical removal of osteochondromas may be necessary if they cause pain, functional impairment, nerve compression, or vascular compromise. Orthopaedic procedures can help correct skeletal deformities and restore joint function.
• Rehabilitation: Physical therapy and occupational therapy can aid in improving mobility, strengthening muscles, and minimising functional limitations.
• Pain Management: Non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesics may be prescribed to manage pain associated with osteochondromas and joint discomfort.
• Genetic Counselling: Individuals diagnosed with HMO and their families can benefit from genetic counselling to understand the inheritance pattern, assess the risk of passing on the condition and explore reproductive options.

Complications

Depending on the location and growth, osteochondromas can cause complications by affecting the growth plates of children, leading to asymmetric growth or deformities. If found on the rib bones, they may lead to perforation of the lungs (pneumothorax), causing difficulty in breathing. If found on the vertebra/ spine, they may cause spinal cord compression and lead to weakness in the limbs, paralysis or even urinary and bowel problems. Other complications include tendon compression, malignant transformation to chondrosarcoma (suspected when there is growth and pain from the lesion after skeletal maturity), fractures through the lesion and recurrence following removal surgery.⁹

Athletes corner

As discussed previously, most osteochondromas are asymptomatic and are found incidentally on x-rays; however, athletes may be symptomatic due to mechanical effects such as the lesion rubbing against adjacent soft tissue and causing inflammation with certain activities such as exercise. In athletes, osteochondrosarcomas are usually found in the knee and present with knee and hip pain and stiffness. For athletes, it is important to have frequent check-ups with your physician. Athletes should never ignore what may appear to be minor symptoms such as tingling and numbness. If pain is experienced with no other concerning symptoms, anti-inflammatory medication (NSAIDS) can be used on an as-required basis with follow-up with the physician. Athletes (symptomatic or symptomatic) may be referred to an orthopaedic clinic for further assessment and possible resection. This is because due to disabling symptoms and in order to allow them to return faster to original sports activities, it is preferable to treat athletes with surgical interventions10. Please note all surgeries come with complications, and in-depth discussions should be had with physicians on the possible effects on athletic activities in the future.

FAQs

How can I prevent HMO?

HMO is a gene mutation, and there is currently no known lifestyle change that can prevent the development of the disease. It is known to be hereditary, although studies show that about 10% of those affected have no family history of HMO.

How common is HMO?

HMO is a rare genetic disorder with a reported incidence of 1 in 50,000.

Who is at risk of HMO?

Those with a strong family history of HMO, children under the age of 12 and usually males are more likely to be diagnosed with HMO.

When should I see a doctor?

Consider seeing a doctor if any of the following symptoms are experienced: pain, numbness, tingling, weakness or urinary/ bladder problems

Summary

HMO is a rare genetic disorder characterised by the development of multiple benign bone tumours. The condition can lead to bone deformities, growth disturbances, and functional limitations. While there is no cure for HMO, appropriate management and treatment strategies can help alleviate symptoms, prevent complications, and improve the quality of life for affected individuals. Early diagnosis, regular monitoring, and a multidisciplinary approach involving orthopaedic interventions and rehabilitation are crucial components of managing HMO. However, if you do experience any of the symptoms above, please seek medical advice.