NORD gratefully acknowledges John B. Mulliken, MD, Co-Director, Vascular Anomalies Center; Director, Craniofacial Center, Boston Children’s Hospital, for assistance in the preparation of this report.
Maffucci syndrome is not recognizable at birth. Lesions usually develop early in childhood, most often between 1-5 years of age. The severity of the disorder is variable. Some patients have a very benign course, whereas others develop serious complications.
The first sign of Maffucci syndrome is usually finding an enchondroma in a long bone. Enchondromas distort and weaken the affected bones, thus initial presentation with a pathologic fracture is common. These cartilaginous tumors cause bulging of the bones, bowing of the arms and legs, and often disproportionate (asymmetric) growth (different lengths of the arms or legs). The patient may exhibit short stature in adulthood. Enchondromas affect only one side of the body in approximately 40 percent of patients.
Vascular lesions on the skin also usually appear in early childhood (around 4-5 years of age) and are often progressive. These lesions do not necessarily occur near the bones that have enchondromas. These vascular lesions begin as compressible, round, bluish spots. In time, they become firm, knotty, warty, and often contain calcium stones (phleboliths). The hand is the most common location; however vascular lesions can also occur in internal structures, such as the membranes that cover the brain and spinal cord (meninges), the tongue, and the oral mucosa.
These vascular lesions used to be called “cavernous hemangiomas”. Microscopic studies have shown that they are comprised of abnormally-formed veins so that the more modern term is “venous malformation.” A benign vascular tumor, designated as “spindle cell hemangioma,” often arises in these malformed veins.
Patients with Maffucci syndrome are at risk to developing a malignant tumor, particularly a tumor of cartilage known as “chondrosarcoma.” The more enchondromas, the higher the risk of malignancy. The frequency has been estimated to be between 15-40 %; however, some investigators believe that chondrosarcoma in Maffucci syndrome is over-reported. Less frequently, other malignant, non-skeletal connective tissue neoplasms can occur in patients with Maffucci syndrome.
In 2011, the cause of Maffucci syndrome was discovered to be a change (mutation) in a gene known as IDH1 (rarely IDH2). The same mutations are found in the related disorder Ollier disease. Since the defect occurs after fertilization (called a somatic mutation), Maffucci syndrome is not considered to be hereditary, that is, it cannot be passed along in a family. The cases occur randomly and there are no known pedigrees of affected family members.
The diagnosis of Maffucci syndrome is made by a detailed history, thorough 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.
Management of Maffucci syndrome is focused on the specific signs/symptoms in the particular affected individual. No intervention is needed for asymptomatic patients. Treatment requires coordinated efforts of a team of specialists (multidisciplinary care). The warty (verrucous) vascular lesions can be injected with a drug that shrinks and hardens the area (sclerosing agent); however, often operative removal is also needed. Enchondromas can be surgically removed (resected) if necessary. A specialist in hand surgery is needed to correct the skeletal abnormalities of the hand if there is loss of function or recurrent fracture. An orthopedic surgeon addresses leg length discrepancy, abnormal curvature of the spine (scoliosis) or other skeletal abnormalities.
A patient with Maffucci syndrome should be regularly monitored because of the risk of malignant transformation of an enchondroma or development of a tumor elsewhere. If a malignancy does not occur, patients with Maffucci syndrome have an otherwise normal life expectancy. A conservative management is recommended for patients with Ollier disease. Operations may be necessary for complications, such as pathologic fracture, growth disturbance, or malignant change.
Ivosidenib is an IDH1 inhibitor and achieved FDA approval for treatment of patients with malignancy. Discussions are ongoing regarding possible use in Maffucci syndrome and Ollier disease.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Contact for additional information about Maffucci syndrome:
John B. Mulliken, MD
Co-Director, Vascular Anomalies Center
Director, Craniofacial Center
Boston Children’s Hospital
300 Longwood Avenue
Boston, MA 02115
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
Biesecker LG. Proteus syndrome. In: Cassidy SB, Allanson JE, editors. Management of Genetic Syndromes. New York: Wiley; 2005: 449-456.
Biesecker L. Proteus Syndrome. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:239.
Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al. Pharmacodynamic study of Miransertib in individuals with Proteus syndrome. Am J Med Genet. 2019;104:484-491
Amary MF, Damato S, Halai D. Ollier disease and Maffucci syndrome are caused by somatic mutations in IDH1 and IDH1. Nature Genet 2011; 43:1262-65.
Pansuriza TC, van Eijk R, D’Amato P, et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondromas and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nature Genet. 2011;43:1256-61.
Campbell SJ, Nguyen NV. Maffucci Syndrome. Medscape. Updated: Jun 07, 2017. http://emedicine.medscape.com/article/1111804-overview Accessed August 1, 2019.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Enchondromatosis, Multiple, Ollier Type. Entry No: 166000. Last Update 05/02/2016. Available at: http://omim.org/entry/166000 Accessed August 1, 2019.
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