Maffucci syndrome ... (Maffucci syndrome) - Genes IDH1 and IDH2

Maffucci syndrome is a disease that primarily affects bones and skin, characterized by the development of multiple endochondromas bone. These growths occur most often in the bones of the extremities, especially in the hands and feet, but can also develop in the skull, ribs and vertebrae. Enchondromas can lead to significant bone deformities, limb shortening and fractures. They develop near the ends of bones where growth occurs, and cease to be formed after the affected people stop growing. Following bone deformities associated with Maffucci syndrome, affected individuals generally have short stature and underdeveloped muscles.

Maffucci syndrome differs from similar alterations involving enchondromas by the presence of hemangiomas. In addition, those affected may have lymphangioma. These growths can appear anywhere on the body. Abnormal growths associated with the disease can become cancerous. In particular, those affected may develop chondrosarcoma, especially in the skull. They also have an increased risk of other cancers such as ovarian cancer or liver. Signs and symptoms of the disease can be detected at birth, but usually do not appear until about five years. People usually have a normal life and intelligence is not affected. The extent of their physical impairment depends on individual skeletal deformities, but in most cases, have significant limitations in their activities.

In most people with Maffucci syndrome, the process is due to mutations in the gene IDH1 (isocitrate dehydrogenase (NADP (+)) 1, cytosolic), located on the long arm of chromosome 2 (2q33.3) or the IDH2 gene (isocitrate dehydrogenase (NADP (+)) 2, mitochondrial), located on the long arm of chromosome 15 (15q26.1). These genes encode enzymes isocitrate dehydrogenase and isocitrate dehydrogenase 1 2, respectively. These enzymes convert isocitrate to -ketoglutarate-2. This reaction generates a NADPH molecule, necessary for many cellular processes and helps protect cells from reactive oxygen species.

Mutations in IDH1 and IDH2 responsible Maffucci syndrome genes found in some cells enchondromas and hemangiomas in people with Maffucci syndrome as well as in bone marrow or blood of a few individuals affected. These mutations prevent the dehydrogenase 1 and 2, isocitrate enzymes carry out its normal activity, the conversion of isocitrate to -ketoglutarate-2. Instead, the altered enzymes acquire a new function, abnormal: the production of a compound called D-2-hydroxyglutarate. Because these genetic changes lead to enzymes with a new function, they are classified as "gain of function mutations." The relationship between mutations and signs and symptoms of the disease is not well understood.

It is likely that the disease may be associated with abnormalities that occur before birth in the development of the ectoderm and mesoderm. In early development, these cell layers form the basis of many of the organs and tissues. Abnormal development of the ectoderm and mesoderm is unknown how results enchondromas growth and other characteristics of Maffucci syndrome. In some people with Maffucci syndrome, enchondromas become cancerous chondrosarcoma.


Maffuci syndrome is not inherited. Mutations responsible for the development of this process are somatic, meaning that occur during the life of a person. A somatic mutation in a single cell. As the cell continues to grow and divide, cells derived therefrom also have the same mutation. Maffucci syndrome is believed that the mutation occurs in a cell at the beginning of development before birth; cells arising from abnormal cell that have the mutation, while other body cells do not, a situation known as mosaicism.


Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Maffucci syndrome by complete PCR amplification of the exons of IDH1 and IDH2, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).