Hereditary multiple osteochondromas (diaphysea aclasis, osteochondromatosis, formerly – hereditary multiple exostoses) is a disorder characterized by the occurrence of numerous osteochondromas.
Hereditary multiple osteochondromas is a rare autosomal dominant condition in which multiple benign bone tumors known as osteochondromas are formed on the ends of the long bones of the limbs. These benign tumors are growing slowly and may limit the range of motions in the extremities, cause pain due to nerve compression and lead to the deformations of the bones. Sometimes the disease is associated with short stature and other skeletal abnormalities. Only in some individuals these outgrowths become malignant and give rise to sarcomas, the risk of malignization is about 1 in 200.
The disorder is caused by the mutations in EXT1 (located on chromosome 8) and EXT2 (on chromosome 11) genes that encode the production of the proteins exostosin-1 and exostosin-2, respectively. These mutations are inherited as autosomal dominant patterns meaning that one copy of the abnormal gene is enough to cause the development of the disease. A person inherits it usually from one parent that is very likely affected as well. Nevertheless, in about one-fifth of cases the disorder is caused by a spontaneous new mutation – a person carrying this mutation is the first one in the family to develop multiple osteochondromas.
About 1 child in 50,000 live birth is born with EXT1/EXT2 mutation. When there is a mutation in the EXT1 gene the disease considered to be of type 1. The presence of the EXT2 gene is characteristic of hereditary multiple exostosis type 2. Type 1 accounts for about two-thirds of the cases and the symptoms seems to be more severe in type 1. However, in about 15% of affected individuals, there is neither EXT1 nor EXT2 mutation and the cause of the disease remains unknown.
Multiple benign (noncancerous) tumors made up of bone tissue and covered by the cartilage known as osteochondromas develop at the end (metaphysis) the long bones of the limbs and on the shoulder blade (scapula) and the hips. Osteochondromas appear as the lumps that can be detected on the extremities and may cause significant deformation of the bones. There are different quantities of exostoses in different individuals, they vary greatly in size and distribution. Typically the lesions develop in childhood by the age of 12 and after puberty, there are no new growths.
Moreover, the bones of the extremities may be shorter than usual due to disrupted bone growth leading to short stature. The length of the right and left limbs is often different, therefore, significant limb length discrepancy is observed.
Numerous tumors may compress the nerves and soft tissues surrounding the neoplasms resulting in pain and limit the range of movements. Some of the bones especially the hip may develop abnormally (hip dysplasia) and lead to walking difficulties. Pelvis involvement may also lead to urinary obstruction.
When the vertebrae are affected spinal cord compression may become an issue and cause a feeling of numbness and muscle weakness or even paralysis.
The diagnosis can be made based on history and assessing the X-rays. It is recommended to repeat the scans each year to detect signs of malignization as soon as possible.
Genetic tests to detect EXT1 and EXT2 genes are also available.
Surgical excision of the tumors may be necessary if they are associated with pain, significant limb deformation or limit normal movement.