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Hereditary multiple exostoses
HME leads to bony lumps, primarily affecting joints like knees and shoulders, which can cause pain, restricted movement, and skeletal deformities. It usually becomes apparent in childhood and affects individuals of all ethnic backgrounds.
Overview
Hereditary multiple exostoses (HME), also known as multiple osteochondromas, is a condition where people develop several benign bone tumours called osteochondromas. These are cartilage-capped bony growths that emerge from the outer surface of bones, most commonly the long bones of the limbs [PMID:17006886]. While these growths are benign, they can cause a range of problems depending on their size and location, such as pain, nerve compression, and changes in skeletal development. The condition typically manifests during childhood, often becoming noticeable as hard, immovable lumps near joints.
Symptoms & clinical features
The primary symptom of HME is the presence of osteochondromas. These bony growths can vary greatly in size and number, from just a few small lumps to many larger ones. They are most frequently found near the ends of long bones, particularly around the knees, shoulders, and ankles [PMID:33604473]. Symptoms can include pain, especially if a growth presses on a nerve, tendon, or blood vessel. Restricted joint movement can also occur if growths interfere with joint function. Other potential issues include limb length discrepancies, bowing of long bones, and joint deformities, which may lead to an altered gait or other functional limitations. In some cases, the osteochondromas may cause cosmetic concerns.
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Affected organs
HME primarily affects the skeletal system. The osteochondromas typically develop on bones that undergo endochondral ossification, which is the process by which most bones in the body are formed from cartilage. This includes the long bones of the arms and legs, as well as flat bones such as the scapulae (shoulder blades) and pelvis. While the growths themselves are benign, their location can impact surrounding tissues. For instance, growths near joints can affect the function of those joints, and growths near nerves or blood vessels can cause compression, leading to symptoms like numbness, weakness, or circulatory problems in the affected limb.
Risks & severity
The severity of HME can vary significantly between individuals, even within the same family. Some people might have only a few small, asymptomatic osteochondromas, while others develop numerous large growths leading to considerable pain and skeletal issues. The main lifetime risk associated with HME is the potential for malignant transformation, meaning an osteochondroma could, in rare cases, develop into a cancerous chondrosarcoma. Research suggests this risk is estimated to be around 0.5% to 5% over a lifetime, with growths in the pelvis or shoulder blade having a slightly higher risk [PMID:33604473]. Most osteochondromas appear and grow during childhood, typically ceasing growth when skeletal maturity is reached. However, new growths can occasionally develop into adulthood.
Genetic causes
Hereditary multiple exostoses is caused by pathogenic variants in either the EXT1 or EXT2 genes. The EXT1 and EXT2 genes provide instructions for making proteins involved in the production of heparan sulphate, a type of sugar molecule found on the surface of cells and in the extracellular matrix. Heparan sulphate plays a crucial role in regulating bone growth and development. When there are pathogenic changes in EXT1 or EXT2, the normal production of heparan sulphate is disrupted [PMID:17006886]. This disruption is thought to lead to abnormal cartilage cell proliferation and differentiation at the growth plates, resulting in the formation of osteochondromas. Approximately 65% of HME cases are attributed to variants in EXT1, and about 25% to variants in EXT2; in some cases, no genetic cause is identified in these genes.
- EXT1 exostosin glycosyltransferase 1
- EXT2 exostosin glycosyltransferase 2
Inheritance pattern
Hereditary multiple exostoses follows an autosomal dominant inheritance pattern. This means that an individual only needs to inherit one copy of an altered EXT1 or EXT2 gene from one parent to develop the condition. If a parent has HME, there is a 50% chance with each pregnancy that their child will also inherit the altered gene and develop the condition. The condition can also arise spontaneously in individuals with no family history, known as a de novo variant. In such cases, the genetic change occurs for the first time in that individual and was not inherited from either parent. If a child has a de novo variant, the risk to their siblings is generally very low.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of HME typically begins with a clinical examination, where a doctor will feel for the characteristic bony lumps. Imaging studies, such as X-rays, are then used to confirm the presence and location of osteochondromas and to assess their impact on bone structure and joint alignment. Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scans may be used for a more detailed assessment, particularly if there are concerns about nerve compression or potential malignant change. A definitive diagnosis is confirmed through genetic testing, which looks for pathogenic variants in the EXT1 and EXT2 genes. In the UK, genetic testing for HME falls under the NHS Genomic Medicine Service, typically initiated following a referral from a specialist paediatrician or orthopaedic surgeon to a clinical genetics service. This testing is often performed under specific R-codes, such as R256 Exostoses.
Management & lifestyle
Management of HME is focused on monitoring the osteochondromas, managing symptoms, and addressing complications. Regular clinical reviews and X-rays are important to monitor the size and number of growths, especially during childhood, and to look for any concerning changes that might suggest malignant transformation. Pain can be managed with over-the-counter pain relievers or, if severe, with specialist pain management. Surgical removal of osteochondromas may be considered if they are causing significant pain, restricting joint movement, compressing nerves or blood vessels, or if there is concern about malignant change. Corrective orthopaedic surgery may also be necessary to address limb length discrepancies or bone deformities. Individuals with HME are supported through the NHS, often involving a multidisciplinary team including orthopaedic surgeons, genetic counsellors, and physiotherapists. Genetic counsellors can provide essential information about the inheritance pattern, recurrence risks, and implications for family planning.
UK care pathway
In the UK, individuals with suspected Hereditary Multiple Exostoses would typically enter the NHS Genomic Medicine Service pathway. This often starts with a referral from a GP or specialist to a clinical genetics service. Here, a genetic counsellor or clinical geneticist will discuss the condition, inheritance patterns, and the appropriateness of genetic testing. Genetic testing for HME, often under an NHS R-code like R256 Exostoses, aims to identify pathogenic variants in the EXT1 or EXT2 genes. This diagnosis helps guide ongoing orthopaedic and surgical management within the NHS, often involving regular surveillance and interventions as needed. Genetic counsellors play a key role in providing information and support to affected individuals and their families.
Frequently asked questions
Are the bone growths (osteochondromas) always painful?
No, not all osteochondromas cause pain. Many individuals with HME have growths that do not cause any discomfort. Pain typically occurs if a growth presses on a nerve, tendon, or blood vessel, or if it interferes with joint movement.
Can the bone growths become cancerous?
There is a small, but recognised, lifetime risk of an osteochondroma transforming into a cancerous chondrosarcoma. Research suggests this risk is between 0.5% and 5%. Regular monitoring is important to detect any changes early.
Will my children inherit Hereditary Multiple Exostoses?
As HME is inherited in an autosomal dominant pattern, if you have the condition, each of your children has a 50% chance of inheriting the altered gene and developing HME. Genetic counselling can provide more personalised information and support for family planning.
When do the bone growths typically stop growing?
Osteochondromas usually appear and grow during childhood, often ceasing to grow once an individual reaches skeletal maturity, typically in their late teens or early twenties. However, new growths can occasionally develop, and existing ones should still be monitored.
What kind of specialist doctor treats HME?
Management of HME typically involves orthopaedic surgeons, who specialise in bone and joint conditions. You might also see a clinical geneticist for diagnosis and genetic counselling, and physiotherapists for support with mobility and physical function.
References
- D'Arienzo A, Andreani L, Sacchetti F. Hereditary Multiple Exostoses: Current Insights. Orthopedic research and reviews. 2019. PMID: 31853203
- Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. Best practice & research. Clinical rheumatology. 2008. PMID: 18328980
- Adam MP, Bick S, Mirzaa GM. Hereditary Multiple Osteochondromas. 1993. PMID: 20301413
- Tepelenis K, Papathanakos G, Kitsouli A. Osteochondromas: An Updated Review of Epidemiology, Pathogenesis, Clinical Presentation, Radiological Features and Treatment Options. In vivo (Athens, Greece). 2021. PMID: 33622860
- Rueda-de-Eusebio A, Gomez-Pena S, Moreno-Casado MJ. Hereditary multiple exostoses: an educational review. Insights into imaging. 2025. PMID: 39982564
- Pacifici M. Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments. Current osteoporosis reports. 2017. PMID: 28466453
- Beltrami G, Ristori G, Scoccianti G. Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern. Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases. 2016. PMID: 27920806
- Bukowska-Olech E, Trzebiatowska W, Czech W. Hereditary Multiple Exostoses-A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies. Frontiers in genetics. 2021. PMID: 34956317