Maffucci Syndrome
Maffucci syndrome is a rare, non-inherited disorder characterized by benign cartilage growths inside the bones and abnormal blood vessel growths in the skin.
Overview & Symptoms
Maffucci syndrome is a rare disorder that primarily affects the bones and the skin. The condition is characterized by the development of multiple enchondromas, which are noncancerous (benign) cartilage growths that form inside the bones. These growths most frequently occur in the limbs—particularly the hands and feet—but can also develop in the skull, ribs, and vertebrae of the spine.
Enchondromas can lead to several physical complications, including:
- Severe bone deformities
- Shortening of the limbs
- Bone fractures
- Short stature and underdeveloped muscles
Signs of Maffucci syndrome may be detectable at birth, though they typically become apparent around age 5. Enchondromas grow near the ends of bones where normal growth occurs, and they usually stop forming once an individual reaches early adulthood and stops growing. The degree of physical impairment varies depending on the severity of the skeletal deformities, but most affected individuals do not experience major limitations in their daily activities.
Skin Growths and Cancer Risks
Maffucci syndrome is distinguished from a similar bone disorder (Ollier disease) by the presence of red or purplish skin growths made of tangled, abnormal blood vessels, known as hemangiomas. Some individuals may also develop lymphangiomas, which are masses formed from lymphatic vessels. These skin and tissue growths can appear anywhere on the body.
While enchondromas begin as benign, they carry a risk of becoming cancerous (malignant). Affected individuals have an increased risk of developing a type of bone cancer called chondrosarcoma, particularly in the skull. There is also an elevated risk of developing other types of cancers, such as ovarian or brain cancers. Despite these risks, individuals with Maffucci syndrome typically have a normal lifespan, and their intelligence is unaffected.
Frequency
Maffucci syndrome is extremely rare. Fewer than 200 cases have been reported worldwide since the condition was first described in 1881.
Causes & Genetic Factors
In most cases, Maffucci syndrome is caused by mutations in the IDH1 or IDH2 genes. These genes provide instructions for making the enzymes isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, which convert isocitrate into a compound called 2-ketoglutarate, producing a vital cellular molecule called NADPH in the process.
Mutations in IDH1 or IDH2 cause these enzymes to take on an abnormal, new function. Although these genetic mutations have been identified in the cells of enchondromas and hemangiomas in people with Maffucci syndrome, the exact process by which they cause the specific signs and symptoms of the disorder is not yet fully understood. Some cases of the syndrome may also be caused by mutations in other, unidentified genes.
Inheritance Pattern
Maffucci syndrome is not inherited. The genetic mutations that cause this disorder are somatic, meaning they occur spontaneously during a person's lifetime in a single cell. As that cell divides, all cells derived from it carry the mutation, while the rest of the body's cells do not. This genetic state is known as mosaicism. In Maffucci syndrome, the somatic mutation is believed to occur early in embryonic development before birth.
Other Names for This Condition
- Chondrodysplasia with hemangioma
- Chondroplasia angiomatosis
- Dyschondroplasia and cavernous hemangioma
- Enchondromatosis with hemangiomata
- Hemangiomata with dyschondroplasia
- Hemangiomatosis chondrodystrophica
- Kast syndrome
- Multiple angiomas and endochondromas