Metachondromatosis

Metachondromatosis is an autosomal dominant, incompletely penetrant genetic disease affecting the growth of bones, leading to exostoses primarily in the hands and feet as well as enchondromas of long bone metaphyses and iliac crests. This syndrome affects mainly tubular bones, though it can also involve the vertebrae, small joints, and flat bones. The disease is thought to affect exon 4 of the PTPN11 gene. The observation of one family with five affected people led to the identification of the disease as autosomal dominant. The symptoms of Metachondromatosis are seen as follows:

Enchondromas are benign tumors present on the inside of bones. In Metachondromatosis, enchondromas involves the iliac crests and metaphyses of long bones, often the proximal femur. Usually, these tumors are painless; however, when present in the hands or feet, or in multiple lesions, as typically seen, bone deformity can occur.

Metachondromatosis is inherited in an autosomal dominant manner, needing only one copy of the defective gene to cause the disorder. This deletion causes a frameshift, resulting in a nonsense mutation with a premature stop codon. This causes severe truncation and loss of function in the gene’s protein product, tyrosine phosphatase SHP 2. which is associated with differentiation in chondrocytes (specialized cells in cartilage tissue). Individuals affected by metachondromatosis generally demonstrate high levels of IHH expression, which is believed to be responsible for the tumor growth. Using radiographic methods, osteochondromas can be seen at the metaphyses of the short tubular bones, such as those in the hands and feet, pointing towards the joints. Enchondromas would also be visible along with the osteochondromas. The differential diagnosis includes hereditary multiple osteochondromas. This is a condition in which the long bones are primarily affected, and the lesions point away from the joint or growth plate. This may also result in the shortening or deformity of the affected bones.

Osteochondromas are usually painless, and in many cases, they spontaneously regress after the first or second decade of life. Most patients are asymptomatic, making medical intervention unnecessary. However, in extreme cases such as severe malalignment of the fingers and toes, surgery can be used to remove the osteochondromas.