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Last updated: 10/10/2023
Years published: 1988, 1990, 1997, 1998, 2007, 2012, 2016, 2019, 2023
NORD gratefully acknowledges John B. Mulliken, MD, Co-Director, Vascular Anomalies Center, Director, Craniofacial Center, Boston Childrenโs Hospital, for assistance in the preparation of this report.
Maffucci syndrome is an extremely rare disorder characterized by benign cartilage overgrowths (enchondromas), skeletal deformities and cutaneous lesions composed of abnormal blood vessels. Enchondromas arise in bones, most frequently in the hands and feet, and less often in the legs and long bones of the arm.
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 often are progressive. These lesions do not necessarily occur near the bones that have enchondromas. Cutaneous vascular lesions begin as compressible, round, bluish spots. In time, they become firm, knotty, warty, and often form 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.
The vascular lesions used to be called โcavernous hemangiomasโ. Microscopic studies have shown that they are comprised of abnormally formed veins; the modern term is โvenous malformation.โ A benign vascular tumor, designated as โspindle cell hemangioma,โ 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 โchondrosarcoma.โ The more enchondromas, the higher the risk of malignancy. The frequency of tumors has been estimated to be between 15-40 %, however, some researchers think chondrosarcoma in Maffucci syndrome is over-reported. Less frequently, other malignant non-skeletal connective tissue neoplasms occur in patients with Maffucci syndrome.
In 2011, the cause of Maffucci syndrome was discovered to be a change (variant or mutation) in a gene known as IDH1 (rarely IDH2). The same gene variants are found in the related disorder Ollier disease. Since the variant occurs after fertilization (called a somatic mutation), Maffucci syndrome is not thought to be hereditary, that is, it cannot be passed along in a family. The cases occur randomly and there are no known families with multiple affected family members.
Maffucci syndrome occurs in all ethnic groups and equally affects males and females.
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.
Treatment
Management of Maffucci syndrome is focused on the specific signs and symptoms in the patient. 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 surgery 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 in the body. If a malignancy does not occur, patients with Maffucci syndrome have an otherwise normal life expectancy. 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 has been FDA approved 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:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about Maffucci syndrome:
John B. Mulliken, MD
Co-Director, Vascular Anomalies Center
Director, Craniofacial Center
Boston Childrenโs 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.
TEXTBOOKS
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.
JOURNAL ARTICLES
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, DโAmato 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.
INTERNET
Campbell SJ, Nguyen NV. Maffucci Syndrome. Medscape. Updated: March 28, 2022. https://emedicine.medscape.com/article/1111804-overview
Accessed Oct 10, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Enchondromatosis, Multiple, Ollier Type. Entry No: 166000. Last Update 05/02/2016. Available at: https://omim.org/entry/166000 Accessed Oct 10, 2023.
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Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report
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