Maffucci syndrome

Summary

(muh-FOO-chee SIN-drome) A very rare disorder that affects the skin and cartilage. It is marked by benign (not cancer) growths of cartilage in bones. These growths usually occur in the hands or feet, but may also occur in the skull, ribs, and spine. They may cause severely deformed bone, shortening of the arms or legs, broken bones, and other bone problems. Maffucci syndrome is also marked by hemangiomas (benign blood vessel tumors) , most often in the skin. People with this syndrome have an increased risk of certain cancers, such as chondrosarcoma (cancer that forms in bone cartilage) or cancers of the ovary or liver. Maffucci syndrome is most common in young children.

Histological image of an enchondroma, a common feature in Maffucci syndrome.

Epidemiology

Maffucci syndrome is very rare. Since it was first described in 1881, fewer than 200 cases have been reported worldwide.

Cause

In most people with Maffucci syndrome, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas and hemangiomas in people with Maffucci syndrome, the relationship between the mutations and the signs and symptoms of the disorder is not well understood.

Mutations in other genes may also account for some cases of Maffucci syndrome.

Inheritance

Maffucci syndrome is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Maffucci syndrome, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism.

Signs and symptoms

It is characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures. Maffucci syndrome is distinguished from a similar disorder that involves enchondromas (Ollier disease) by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). In addition to hemangiomas, individuals with Maffucci syndrome occasionally also have lymphangiomas, which are masses made up of the thin tubes that carry lymph fluid (lymphatic vessels). These growths may appear anywhere on the body.

Although the enchondromas associated with Maffucci syndrome start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Maffucci syndrome also have an increased risk of other cancers, such as ovarian or liver cancer. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Hemangiomatosis
• Multiple enchondromatosis
• Osteolysis(Breakdown of bone)
• Venous thrombosis(Blood clot in vein)

30%-79% of people have these symptoms

• Bone pain
• Exostoses(Formation of new noncancerous bone on top of existing bone)
• Scoliosis
• Short stature(Decreased body height)
• Subcutaneous nodule(Firm lump under the skin)

5%-29% of people have these symptoms

• Astrocytoma
• Breast carcinoma(Breast cancer)
• Cerebral palsy
• Chondrosarcoma
• Cranial nerve paralysis
• Dysphagia(Poor swallowing)
• Goiter(Enlarged thyroid gland in neck)
• Neoplasm of the adrenal cortex
• Ovarian neoplasm(Ovarian tumor)
• Parathyroid adenoma
• Pituitary adenoma(Noncancerous tumor in pituitary gland)
• Recurrent fractures(Increased fracture rate)

Diagnosis

The diagnosis of Maffucci syndrome is made by physical examination and radiologic assessment.Surgical removal and microscopic study of the skeletal lesions confirm the presence of enchondroma and distinguish the tumor from chondrosarcoma.

Treatment

Management aims at relief of symptoms and early detection of malignancies. Individuals with Maffucci syndrome may benefit from consultations with the following specialists: Radiologist: Radiography or CTscanning performed periodically to evaluate bone changes. Orthopedic surgeon: An orthopedic surgeon may be consulted to evaluate bone changes and skeletal neoplasms and to help in treatment of fractures associated with the disease. Dermatologist: A dermatologist may be consulted to evaluate hemangiomas associated with the condition and to identify any new lesions on the skin.

Related Pages

• Enchondroma
• Hemangioma
• Chondrosarcoma
• Skeletal dysplasia

NIH genetic and rare disease info

• NIH info on Maffucci syndrome

Maffucci syndrome is a rare disease.

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