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About 250 cases worldwide have been reported in the literature so far. The disease affects both males and females.

Symptoms are present usually in childhood, but may occur at birth, during infancy or, rarely, at a later age. Vascular anomalies are diagnosed a median of 2 years after the enchondromas. Because of this, it may be misdiagnosed as Ollier disease. Moreover, fewer than 15% of patients with Maffuci syndrome are diagnosed with vascular anomalies before the age of 1 year. Enchondromas are commonly found in the bones of the hands and feet, as well as the femur, tibia, fibula, and pelvis, rarely the humerus, ribs, and skull. Lesions are asymmetrically distributed and may be uni- or bilateral. This asymmetric distribution may result in bones deformities which include asymmetrical growth, limb length inequality or angular deformity (genu varum or genu valgum). Functional impairment and deformities may cause fractures in some patients. Soft tissue, visceral, or cutaneous hemangiomas manifest as blue subcutaneous nodules. Rarely, lymphangiomas or phlebectasias may be found. Hemangiomas can be uni- or bilateral and are generally asymmetric with wide distribution and reported locations including the leptomeninges, eyes, pharynx, tongue, trachea, and intestines. The disease course tends to be slow, with bone and skin abnormalities resolving in the second or third decade of life. There is however a risk of malignant progression from enchondromas to chondrosarcoma in adulthood. Hemangiomas can also become malignant in about 8.5% of cases. Other reported malignancies include pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, as well as glioma, astrocytoma, and sarcomas.

Somatic mutations in IDH1 (2q34) and IDH2 (15q26.1) have been identified in affected tissue (enchondromas or spindle cell hemangiomata) of most tested patients. No familial case has been reported.

The diagnosis is based on the characteristic occurrence of enchondromas and hemangiomas. As in Ollier disease, diagnosis of enchondromas is based on clinical and conventional radiological evaluations. Enchondromas appear as radiolucent defects that originate in the metaphyses.

Ollier disease is the main differential diagnosis.

Management and treatment aim to relieve symptoms and are not indicated in asymptomatic patients. Regular examinations by an orthopedic surgeon and dermatologist to evaluate changes in the skin and bone lesions are mandatory. Annual monitoring of malignant transformation is recommended. No specific therapy exists to treat the disease. Surgery is at present the only option when complications occur.

Depending on the extent of skeletal involvement, Maffucci syndrome may result in severe deformities with functional and quality of life repercussions. Life span depends on malignant transformation but is otherwise normal. Prognosis is difficult assess because of wide clinical expression and variability, and low prevalence of the disease.