Hereditary multiple exostoses (HME), also called hereditary multiple osteochondromas (HMO), is a condition that is estimated to affect 1 in 50,000 individuals. Multiple benign or noncancerous bone tumors develop in the affected individuals. The number and location vary among affected patients. Most people seem unaffected at birth; however, by the age of 12 years, they develop multiple exostoses.

Hereditary multiple exostoses (HME or MHE), also known as diaphyseal aclasis, is a rare medical condition in which multiple bony spurs or lumps (also known as exostoses, or osteochondromas) develop on the bones of a child. HME is synonymous with multiple hereditary exostoses and multiple osteochondromatosis, which is the preferred term used by the World Health Organization.

HME is an autosomal dominant hereditary disorder. This means that a patient with HME has a 50% chance of transmitting this disorder to his or her children. Most individuals with HME have a parent who also has the condition, however, approximately 10% -20% of individuals with HME have the condition as a result of a spontaneous mutation and are thus the first person in their family to be affected.

HME has thus far been linked with mutations in three genes.

- EXT1 which maps to chromosome 8q24.1

- EXT2 which maps to 11p13

- EXT3 which maps to the short arm of Chromosome 19 (though its exact location has yet to be precisely determined)

Mutations in these genes typically lead to the synthesis of a truncated EXT protein which does not function normally. It is known that EXT proteins are important enzymes in the synthesis of heparan sulfate; however the exact mechanism by which altered synthesis of heparan sulfate that could lead to the abnormal bone growth associated with HME is unclear. It is thought that normal chondrocyte proliferation and differentiation may be affected, leading to abnormal bone growth. Since the HME genes are involved in the synthesis of a glycan (heparan sulfate), HME may be considered a congenital disorder of glycosylation according to the new CDG nomenclature suggested in 2009.

For individuals with HME who are considering starting a family, preimplantation genetic testing and prenatal diagnosis are available to determine if their unborn child has inherited the disease. HME has a 96% penetrance, which means that if the affected gene is indeed transmitted to a child, the child will have a 96% of actually manifesting the disease, and 4% chance of having the disease but never manifesting it. It should be noted that the 96% penetrance figure comes from one study. Other studies have observed both incomplete and variable penetrance but without calculating the % penetrance, e.g. In both the aforementioned studies the symptomless individuals carrying the faulty gene were predominantly female, leading to speculation that incomplete penetrance is more likely to be exhibited in females. Indeed, other work has shown that boys/men tend to have worse disease than females, as well as that the number of exostoses in affected members of the same family can vary greatly. It is also possible for females to be severely affected.

Symptoms are more likely to be severe if the mutation is on the "ext1" gene rather than "ext2" or "ext3"; "ext1" is also the most commonly affected gene in patients of this disorder.

Osteochondromas or osteocartilaginous exostoses are the most common benign tumors of the bones.

The tumors take the form of cartilage-capped bony projections or outgrowth on the surface of bones (exostoses). It is characterized as a type of overgrowth that can occur in any bone where cartilage forms bone. Tumors most commonly affect long bones in the leg, pelvis, or scapula (shoulder blade). Development of osteochondromas take place during skeletal growth between the ages of 13 and 15 and ceases when the growth plate fuses at puberty. They arise within the first three decades of life affecting children and adolescents.

Osteochondromas occur in 3% of the general population and represent 35% of all benign tumors and 8% of all bone tumors. Majority of these tumors are solitary non-hereditary lesions and approximately 15% of osteochondromas occur as hereditary multiple osteochondromas (HMOs). They can occur as a solitary lesion (solitary osteochondroma) or multiple lesions within the context of the same bone (Multiple Osteochondroma). Osteochondromas do not result from injury and the exact cause remains unknown. Recent research has indicated that multiple osteochondromas is an autosomal dominant inherited disease. Germ line Mutations in "EXT1" and "EXT2" genes located on chromosomes 8 and 11 have been associated with the cause of the disease.

The treatment choice for osteochondroma is surgical removal of solitary lesion or partial excision of the outgrowth, when symptoms cause motion limitations or nerve and blood vessel impingements.

Osteochondromatosis is a condition involving a proliferation of osteochondromas.

Types include:

- Hereditary multiple exostoses

- Synovial osteochondromatosis

Osteogenesis imperfecta is a rare condition in which bones break easily. There are multiple genetic mutations in different genes for collagen that may result in this condition. It can be treated with some drugs to promote bone growth, by surgically implanting metal rods in long bones to strengthen them, and through physical therapy and medical devices to improve mobility.

Evidence for exostosis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Exostosis has been reported in dinosaur fossils from several species, including "Acrocanthosaurus atokensis", "Albertosaurus sarcophagus", "Allosaurus fragilis", "Gorgosaurus libratus", and "Poekilopleuron bucklandii".

"Achondroplasia" is a type of autosomal dominant genetic disorder that is the most common cause of dwarfism. Achondroplastic dwarfs have short stature, with an average adult height of 131 cm (4 feet, 3 inches) for males and 123 cm (4 feet, 0 inches) for females.

The prevalence is approximately 1 in 25,000 births.

Limited normal functions and movements are caused by osteochondromas growing slowly and inwardly. The majority of osteochondromas are symptomless and are found incidentally. Each individual with osteochondroma may experience symptoms differently and most of the time individuals will experience no symptoms at all. Some of the most common symptoms are a hard immobile painless palpable mass, adjacent muscle soreness, and pressure or irritation with heavy exercising.

Major symptoms arise when complications such as fractures, bone deformity or mechanical joint problems occur. If the occurrence of an osteochondroma is near a nerve or a blood vessel, the affected limb can experience numbness, weakness, loss of pulse or color change. Periodic changes in the blood flow can also take place. Approximately 20% of patients experiencing nerve compression commonly acknowledge vascular compression, arterial thrombosis, aneurysm, and pseudoaneurysm. Formation of pseudoaneurysm and venous thrombosis lead to claudication, pain, acute ischemia, and symptoms of phlebitis. If the tumor is found under a tendon, it can cause pain during movement causing restriction of joint motion. Pain can also occur due to bursal inflammation, swelling or fracture at the base of the tumor stalk. Some of the clinical signs and symptoms of malignant osteochondroma are pain, swelling, and mass enlargement.

They are more common in males than females, occurring in a ratio of about 5:1. They are strongly associated with the presence of torus mandibularis and torus palatinus.

NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal-cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmar and plantar pits.

One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.

Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.

Some affected individuals are born with an inward- and downward-turning foot (a clubfoot). An abnormality of the kneecap called a double-layered patella is also relatively common. Although some people with recessive multiple epiphyseal dysplasia have short stature as adults, most are of normal height. The incidence is unknown as many cases are not diagnosed due to mild symptoms.

Bone lesions are caused by an imbalance of regulatory factors, characterized by an increased depletion and resorption of old bone tissue and a decrease in bone rebuilding, known as bone remodeling. This imbalance is due to a flooding of regulatory factors released by specific tumors, thus overwhelming the tissue repair system and resulting in these lesions. The over-activity of osteoclasts can also cause hypercalcemia, which can cause damage to the kidneys and requires additional medication and monitoring.

In multiple myeloma, an increased number of myeloma cells block osteoblasts from creating new bone, while these cancerous cells also release factors that cause an upregulation on osteoclasts, causing an increasing in bone tissue resorption and an overall breakdown of bone integrity. This breakdown often begins in the bone marrow near tumor sites and spreads outward to the surface of the implicated bone.

The most common cancers that metastasize to osteolytic lesions are prostate, thyroid, lung and breast, though any cancer can cause bone lesions. Lesions are most often found in larger bones, such as the skull, pelvis, radius, and femur.

Why buccal exostoses form is unclear, but it may involve bruxism (tooth clenching and grinding), and genetic factors. Typically they first appear in early adulthood.

Mutations in the SLC26A2 (DTDST) gene, located at human chromosome 5q32-33.1, are the cause of ARMED. It is considered a milder disorder within a spectrum of skeletal disorders caused by mutations in the gene, which encodes a protein that is essential for the normal development of cartilage and its conversion to bone. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in associated skeletal maldevelopment.

The disorder is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 5 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Maffucci syndrome is a sporadic disease characterized by the presence of multiple enchondromas associated with multiple hemangiomas. Also lymphangiomas may be apparent.

Patients are normal at birth and the syndrome manifests during childhood and puberty. The enchondromas affect the extremities and their distribution is asymmetrical. The most common sites of enchondromas are the metacarpal bones and phalanges of the hands. The feet are less commonly afflicted.

Disfigurations of the extremities are a result. Pathological fractures can arise in affected metaphyses and diaphyses of the long bones and are common (26%).

The risk for sarcomatous degeneration of enchondromas, hemangiomas, or lymphangiomas is 15-30% in the setting of Maffucci syndrome. Maffucci syndrome is associated with a higher risk of CNS, pancreatic, and ovarian malignancies. Multiple enchondromas may present in 3 disorders: Ollier disease, Maffucci syndrome, and metachondromatosis. It is important to make the distinction between these diseases, particularly Ollier disease and Maffucci syndrome. Ollier disease is more common than Maffucci syndrome, and presents with multiple enchondromas often in a unilateral distribution. However, hemangiomas and lymphangiomas are not seen in Ollier disease. Metachondromatosis demonstrates autosomal-dominant transmission and presents with both multiple osteochondromas and enchondromas.

Biophosphonates are drugs that are used to prevent bone mass loss and are often used to treat osteolytic lesions. Zoledronic acid (Reclast) is a specific drug given to cancer patients to prevent the worsening of bone lesions and has been reported to have anti-tumor effects as well. Zoledronic acid has been clinically tested in conjunction with calcium and vitamin D to encourage bone health. Denosumab, a monoclonal antibody treatment RANKl inhibitor that targets the osteocyte apoptosis regualtory RANKL gene, is also prescribed to prevent bone metastases and bone lesions. Most biophosphonates are co-prescribed with disease-specific treatments, such as chemotherapy or radiation for cancer patients.

Osteophyte formation has been classically related to any sequential and consequential changes in bone formation that is due to aging, degeneration, mechanical instability, and disease (such as diffuse idiopathic skeletal hyperostosis). Often osteophytes form in osteoarthritic joints as a result of damage and wear from inflammation. Calcification and new bone formation can also occur in response to mechanical damage in joints.

Multiple familial trichoepithelioma (also known as Brooke–Spiegler syndrome and epithelioma adenoides cysticum) is a cutaneous condition characterized by multiple cystic and solid nodules appearing on the face.

Osteophytes form because of the increase in a damaged joint's surface area. This is most common from the onset of arthritis. Osteophytes usually limit joint movement and typically cause pain.

Osteophytes form naturally on the back of the spine as a person ages and are a sign of degeneration in the spine. In this case, the spurs are not the source of back pains, but instead are the common symptom of a deeper problem. However, bone spurs on the spine can impinge on nerves that leave the spine for other parts of the body. This impingement can cause pain in both upper and lower limbs and a numbness or tingling sensations in the hands and feet because the nerves are supplying sensation to their dermatomes.

Spurs can also appear on the feet, either along toes or the heel, as well as on the hands. In extreme cases, bone spurs have grown along a person's entire skeletal structure: along the knees, hips, shoulders, ribs, arms and ankles. Such cases are only exhibited with multiple exostoses.

Osteophytes on the fingers or toes are known as Heberden's nodes (if on the distal interphalangeal joint) or Bouchard's nodes (if on the proximal interphalangeal joints).

Osteophytes may also be the end result of certain disease processes. Osteomyelitis, a bone infection, may leave the adjacent bone with a spur formation. Charcot foot, the neuropathic breakdown of the feet seen primarily in diabetics, can also leave bone spurs that may then become symptomatic.

When a patient has multiple abnormalities (multiple anomaly, multiple deformity), they have a congenital abnormality that can not be primarily identified with a single system of the body or single disease process. Most medical conditions can have systemic sequelae, but multiple abnormalities occur when the effects on multiple systems is immediately obvious.

Brooke-Spiegler syndrome is a condition where multiple skin tumors develop from skin structures. Tumors commonly occurring in this syndrome include spiradenomas, trichoepitheliomas, and cylindromas. The tumors are generally benign, but may become malignant. Affected individuals are also at increased risk of developing tumors in tissues other than skin – particularly benign or malignant tumors of the salivary glands.

Tumours in Brooke-Spiegler typically appear in early adulthood and are most often found on the head and neck. In severe cases, the tumors may affect vision or hearing. They can be disfiguring and may contribute to depression or other psychological problems. For unclear reasons, females are often more severely affected than males.

Brooke-Spiegler is rare and its exact incidence is unknown.

It is inherited in an autosomal dominant fashion.

Radioulnar synostosis is one of the more common failures of separation of parts of the upper limb. There are two general types: one is characterized by fusion of the radius and ulna at their proximal borders and the other is fused distal to the proximal radial epiphysis. Most cases are sporadic, congenital (due to a defect in longitudinal segmentation at the 7th week of development) and less often post-traumatic, bilateral in 60%, and more common in males. Familial cases in association with autosomal dominant transmission appear to be concentrated in certain geographic regions, such as Sicily.

The condition frequently is not noted until late childhood, as function may be normal, especially in unilateral cases. Increased wrist motion may compensate for the absent forearm motion. It has been suggested that individuals whose forearms are fixed in greater amounts of pronation (over 60 degrees) face more problems with function than those with around 20 degrees of fixation. Pain is generally not a problem, unless radial head dislocation should occur.

Most examples of radioulnar synostosis are isolated (non-syndromic). Syndromes that may be accompanied by radioulnar synostosis include X chromosome polyploidy (e.g., XXXY) and other chromosome disorders (e.g., 4p- syndrome, Williams syndrome), acrofacial dysostosis, Antley–Bixler syndrome, genitopatellar syndrome, Greig cephalopolysyndactyly syndrome, hereditary multiple osteochondromas (hereditary multiple exostoses), limb-body wall complex, and Nievergelt syndrome.

Craniosynostosis (from cranio, cranium; + syn, together; + ostosis relating to bone) is a condition in which one or more of the fibrous sutures in an infant skull prematurely fuses by turning into bone (ossification). Craniosynostosis has following kinds: scaphocephaly, trigonocephaly, plagiocephaly, anterior plagiocephaly, posterior plagiocephaly, brachycephaly, oxycephaly, pansynostosis.

Subungual exostoses are bony projections which arise from the dorsal surface of the distal phalanx, most commonly of the hallux.