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.

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".

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.

Osteochondrodysplasia or skeletal dysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro").

Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia.

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.

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.

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.

A buccal exostosis (also termed alveolar exostosis), is an exostosis (bone prominence) on the buccal surface (cheek side) of the alveolar ridge of the maxilla or mandible. Some consider them a variation of normal anatomy rather than a disease.

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

Surgical excision is common and is a very effective mode of treatment.

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.

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.

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.

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.

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

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.

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.

Lipomatosis is believed to be an autosomal dominant condition in which multiple lipomas are present on the body. Many discrete, encapsulated lipomas form on the trunk and extremities, with relatively few on the head and shoulders. In 1993, a genetic polymorphism within lipomas was localized to chromosome 12q15, where the HMGIC gene encodes the high-mobility-group protein isoform I-C. This is one of the most commonly found mutations in solitary lipomatous tumors but lipomas often have multiple mutations. Reciprocal translocations involving chromosomes 12q13 and 12q14 have also been observed within.

Although this condition is benign, it can sometimes be very painful depending on location of the lipomas. Some patients who are concerned with cosmetics seek removal of individual lipomas. Removal can include simple excision, endoscopic removal, or liposuction.

Other entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, benign symmetric lipomatosis (Madelung disease),Dercum's Disease, familial lipodystrophy, hibernomas, epidural steroid injections with epidural lipomatosis, and familial angiolipomatosis.

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.

Treatment is usually supportive treatment, that is, treatment to reduce any symptoms rather than to cure the condition.

- Enucleation of the odontogenic cysts can help, but new lesions, infections and jaw deformity are usually a result.

- The severity of the basal-cell carcinoma determines the prognosis for most patients. BCCs rarely cause gross disfigurement, disability or death .

- Genetic counseling

An osteolytic lesion (from the Greek words for "bone" (ὀστέον), and "to unbind" (λύειν)) is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal chord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.