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Maffucci¹s syndrome

Synonyms: 

Discussion:

Maffucci's syndrome is a nonhereditary syndrome characterized by multiple hemangiomas and enchondromas, first reported by Dr. Angelo Maffucci in 1881 after a 40-year-old woman died from complications following amputation of an arm. Dr. Maffucci (Oct. 27, 1847 - Nov 24, 1903) was an Italian pathologist born in Calitri, Italy. In 1872 he received his doctorate at  Naples and later was a professor of pathology in Messina  (1882), Catania (1883) and Pisa (1884). At the University of Pisa, he became the school's first director of pathologicalanatomy, and he remained there until his death in 1903.

Enchondromas are benign noncancerous growths of cartilage in bones or in other areas where cartilage is not normally found.

"When multiple enchondromas coexist, the diagnosis of enchondromatosis should be considered.

Multiple enchondromas may occur in 3 distinct disorders:

Diagnosis: 

Prevelance: 

Maffucci syndrome is rare. Fewer than 100 cases have been reported in the United States.

IInternational

Maffucci syndrome is rare, with about 160 total case reports in the English literature.

Symptoms:

Complications:

Treatment:

Pat O'Connor

June 8, 2008

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Maffucci¹s syndrome

What is Maffucci syndrome?

Maffucci syndrome is a disorder that primarily affects the bones and skin. It is characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop on the bones. These growths most commonly occur in the limb bones, especially in the hands and feet; however, they may also occur in the skull, ribs, and vertebrae. Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures. They develop near the ends of bones, where growth occurs, and enchondromas stop forming after affected individuals stop growing. As a result of the bone deformities associated with Maffucci syndrome, people with this disorder generally have short stature and underdeveloped muscles.

Maffucci syndrome is distinguished from similar disorders involving enchondromas by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas). Affected individuals 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.

The abnormal growths associated with Maffucci syndrome may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. They also have an increased risk of other cancers, such as ovarian or liver cancer.

Maffucci syndrome is believed to be present from birth (congenital) in affected individuals. The signs and symptoms of the disorder may be detectable at birth, although they generally do not become apparent until around age five. People with this disorder usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.

How common is Maffucci syndrome?

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

What other names do people use for Maffucci syndrome?

http://ghr.nlm.nih.gov/condition/maffucci-syndrome

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Maffucci¹s syndrome

Poels J
Radiology, New Cross Hospital, Wednesfield Road, WV10 0QP Wolverhampton 
UNITED KINGDOM
poels@doctors.org.uk
 
Patient
Age: 31 year(s)
Sex: M
 
Clinical History and Imaging

The patient, known to have Maffucci's syndrome, was referred to the Orthopaedic Clinic having moved to the area. Initial diagnosis was as a young child. No recent changes had occurred. Clinical examination revealed limb deformities, predominantly in the hands. Blue, subcutaneous haemangiomas, and hard masses adherent to bone were visible and palpable. Plain radiographs of the hands were obtained as a baseline for comparison if a change were to happen.

 
Discussion

Maffucci's syndrome is multiple enchondromas with subcutaneous haemangiomas. The presence of haemangiomas distinguish it from Ollier's disease. It has been suggested that Ollier's disease and Maffucci's syndrome may be part of the same spectrum of mesenchymal dysplastic disorders. The hands are the most common site affected, and there is a tendency for the haemangiomas to predominate on one side of the body. The disease is sporadic with no apparent hereditary component. It manifests in early childhood at an average age of 2.6 years. Enchondromas arise in the medulla of the phalanges and metacarpals, most commonly, and they have the capacity to undergo malignant change. Enchondromas are lytic and expansile with flecks of calcification, described as "popcorn like".

They appear as lobulated, high signal lesions with a low signal rim on T2 weighted magnetic resonance images. Small flecks of signal void caused by the calcification are seen. Haemangiomas are seen on plain radiographs when they calcify. They are seen on T1 weighted MR images as poorly marginated and infiltrative with low to intermediate signal. On T2 weighted images they are of fat density with serpentine flow voids in areas of high flow. Non skeletal tumours are also common, normally of mesoderm origin and often malignant.

It is important to distinguish Maffucci's syndrome from Ollier's disease because of the higher incidence of chondrosarcoma and non skeletal malignancies. A quarter of people with Ollier's disease will have a chondrosarcoma by the age of 40 years, but chondrosarcoma is inevitable with Maffucci's syndrome, normally in the fourth decade. Astrocytoma is the most common non skeletal malignancy, with ovarian and other abdominopelvic tumours also frequently seen. The brain, abdomen and pelvis should be screened by periodic clinical assessment and imaging. Any new pain or change in size of an enchondroma which had been unchanged since adolescence requires careful evaluation. Radiological signs of malignant change include rapid increase in size, deep endosteal scalloping, cortical destruction and periosteal reaction.

 
Diagnosis

Maffucci's syndrome

MESH = A02.835.232 C05.116.099.708.338
 
References

Albregts AE, Rapini RP.
Malignancy in Maffucci's syndrome.
Dermatol Clin. 1995;13:73-8.

Schwartz HS, Zimmerman NB, Simon MA et al.
The malignant potential of enchondromatosis.
J Bone Joint Surg Am. 1987;69:269-74.

Kaplan RP, Wang JT, Amron DM, Kaplan L.
Maffucci's syndrome: two case reports with a literature review.
J Am Acad Dermatol. 1993;29:894-9.

Ahmed SK, Lee WC, Irving RM, Walsh AR.
Is Ollier's disease an understaging of Maffucci's syndrome?
J Laryngol Otol. 1999;113:861-4.

Stoker DJ, Saifuddin A.
Bone tumours (1): general characteristics, benign lesions.
In Grainger RG, Allison DJ, Adam A, Dixon AK (eds) Grainger and Allison's Diagnostic Radiology, Fourth Edition
Churchill Livingstone 2001;1835-1868

 

*Link no longer available

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MaffucCi’s Syndrome: Report of a Case

and Review of the Literature

Nadia S. Al-Hawashim, FRCPA; Younes N. Bakri, MD

Enchondromatosis is a nonhereditary skeletal disorder, characterized by the persistence of cartilage in several bones that are formed by enchondral ossification. In 1900, Ollier described a condition that resembled the osseous component of the syndrome that Maffucci had described 19 years earlier. In Maffucci’s syndrome (MS), the enchondromas coexist with cutaneous and sometimes visceral hemangiomas. Fewer than 200 cases of Maffucci’s syndrome have been published in the English literature.

Malignant transformation of the skeletal lesions is a common feature of MS, and has been observed in approximately 30% of reported cases, with chondro-sarcomas being the most common.1 The development of various types of neoplasms is a well-known complication of MS, and is recognized as a principal factor affecting prognosis. In 1948, Kuzma and King2 first reported an ovarian mesenchymal tumor associated with MS, and since then, sporadic reports have referred to ovarian tumors of sex-cord stromal derivation in patients with enchondromatosis.3-13 We describe the first case of bilateral ovarian serous cystadenomas and polycystic ovarian disease in a patient with MS, and review previously reported gynecologic pathology seen in association with enchondromatosis.

Case Report

A 19-year-old single woman known to have Maffucci’s syndrome, with a three-year history of right flank pain, was referred to our institution for evaluation and management of a pelvic abdominal mass that was suspected of being a juvenile granulosa cell tumor. Menarche occurred at the age of 15 years, and no menstrual disturbances were noted. The family history revealed that no other family member was affected. Deformities and multiple enchondromas were more conspicuous in the left hemiskeleton than in the right. A subcutaneous soft tissue mass in the left arm was

From the Departments of Pathology and Gynecologic Oncology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia.

Address reprint requests and correspondence to Dr. Al-Hawashim: Department of Pathology, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426, Saudi Arabia.

Accepted for publication 31 March 2000. Received 23 November 1999.

diagnosed in early infancy, and had been removed when the patient was six years old. Subsequently, she underwent above-elbow amputation of the left arm for a large disfiguring mass eight months prior to her current presentation. The surgery had been performed at another hospital, and the histology of this mass was not available for review. She had a history of excision of two other subcutaneous hemangiomas.

Laboratory data showed hemoglobin of 10.29 g/dL (normal value, 12.09-16.0 g/dL), with microcytic and hypochromic anemia. Selected tumor markers, including estradiol concentration 164 pmol/L (normal value, 48-903 pmol/L), human chorionic gonadotropin <2.0 IU/L (0.00-10.00 IU/L), and alpha fetoprotein 3.7 µg/L (0.00-10.00 µg/L), were within normal limits. Radiologic examination, including CT scan and MRI of abdomen, showed a multilocular cystic mass extending above the umbilicus. The spleen and abdominal wall showed vascular malformations. Chest scan showed a hemangioma in the lung less than 1 cm in diameter. Exploratory laparotomy showed bilateral ovarian masses without ascites. Left salpingo-oophorectomy and wedge resection of the right ovary were performed. There was no evidence of intra-abdominal spread. Postoperative recovery was uneventful, and the patient was discharged and given an appointment for follow-up.

Pathology

Tissue available for pathologic examination included the left ovarian cystic mass with attached fallopian tube, and two wedge biopsy specimens from the right ovary. The left ovarian cyst was 20 cm in maximal dimension. It was unilocular and the internal surface was smooth gray and lacked any solid or papillary growth. The fallopian tube was stretched over the cyst but was otherwise normal. The two wedge resections from the right ovary measured 4.5 cm and 3.5 cm in maximal dimension. The cut surface revealed multiple cysts ranging in size from barely visible to 1.0 cm in maximal dimension. The intervening tissue was whitish and solid.

Microscopic examination of the left ovary showed ovarian tissue containing numerous primordial follicles and some cystic follicles (Figure 1). Multiple atretic follicles were identified but no corpora lutea or albicantia were seen.
Figure 1. Left ovary with two follicular cysts (H&E, 40x).

Figure 3. Right ovary with two follicular cysts and part of the wall of the serous cystadenoma (H&E, 40x).

The ovarian stroma showed foci of prominent smooth muscle proliferation, and the ovarian cortex was very thick and fibrous. The large cyst was lined by a single layer of cuboidal-to-low columnar ciliated epithelial cells (Figure 2). There was no evidence of any stratification or nuclear atypia. The underlying stroma was dense and fibrous. The two wedge resections from the right ovary showed numerous cystic follicles lined by granulosa cells and having an outer thicker layer of luteinized theca interna cells (Figure 3). The right ovary showed a multilocular cystic lesion, with a lining of a single layer of cuboidal-to-low columnar ciliated epithelial cells. The ovarian stroma showed areas of hyperthecosis, edema and prominent irregular vascular spaces (Figure 4). Few inclusion cysts were seen, with some showing tubal metaplasia. No corpora lutea or albicantia were identified. The diagnosis of synchronous bilateral ovarian serous cystadenomas and polycystic ovarian disease was made.

Figure 2. Wall of the cyst from left ovary showing ciliated single epithelial cell lining (H&E, 100x).

Figure 4. Right ovary with prominent vascular pattern of the stroma (H&E, 100x).

Discussion

Ollier’s disease (OD) is a rare nonhereditary congenital syndrome characterized by multiple enchondromas. When the latter are associated with multiple hemangiomas, the designation Maffucci’s syndrome (MS) is used. The emergence of several neoplasms is a well-known complication of both these diseases, and is recognized as a principal factor affecting patient prognosis. Although chondrosarcoma is by far the most common sarcoma seen in MS,1 a wide variety of non-cartilaginous tumors have been reported. Some enchondromas have been reported to develop into osteosarcoma or dedifferentiated chondrosarcoma.14-18

One of the earliest studies was conducted by Lewis and Ketchum.4 In their extensive review of the world literature of 105 cases of patients who had MS, they found that 15% of them developed chondrosarcoma. Among the various neoplasms which they described, five were gynecologic, two were described as malignant mesenchymal ovarian tumors, one was ovarian thecoma, one was uterine polyp, and another one was uterine fibroid.

In their tri-institutional retrospective study with long-term follow-up, Schwartz et al.19 identified 44 patients with multiple enchondromas. One patient developed an ovarian granulosa cell tumor. They found no evidence of hereditary transmission or of a familial tendency to this syndrome. In addition, they compared the risk of development of malignant neoplasms in patients with MS and those with OD.

The risk of the development of a skeletal or non-skeletal malignant neoplasm for patients with MS is probably close to 100% if they are followed for a long enough period. The risk of the development of a malignant neoplasm in patients with OD is considerably less. In 1993, Kaplan et al.20 reviewed 65 cases of MS. They found that 37% had a malignant lesion, and chondrosarcoma occurred in 30%. There were four cases of ovarian tumors, three mesenchymal (one juvenile granulosa cell tumor, one fibrosarcoma and one adenosarcoma), and one was an adenofibroma. They also found that the number of non-mesodermal tumors was high at 30% (14/49), contrary to the usual belief that MS is mainly a mesodermal dysplasia.

Because the ovarian neoplasm most commonly documented in association with enchondromatosis is juvenile granulosa cell tumor (JGCT), our case was referred with a strong suspicion of this diagnosis. At least 14 cases of JGCT have been reported in association with enchondromatosis, four associated with MS, and the rest with OD.2-13 The accumulation of cases developing ovarian JGCT indicates that this neoplasm appears to be the next most frequent tumor occurring in patients with enchondromatosis. The clinical and morphological features of the tumors and their behavior have not differed significantly from those of JGCTs occurring in patients without these syndromes.12 Single examples of ovarian fibroma21 and fibrosarcoma22 have also been reported in patients with MS. The patient with the fibrosarcoma, who was 17 years old, was re-explored 18 months after left oophorectomy, and there was no evidence of metastatic tumor.

Polycystic ovarian disease has not been previously described in association with MS. Although our patient did not have clinical manifestations of polycystic ovarian disease, it is possible that this was the primary pathology, and the development of bilateral epithelial neoplasms was a secondary phenomenon. This idea was considered by Resta et al.,23 who found that hyperplastic and metaplastic changes of the ovarian surface epithelium and related inclusion cysts can be regarded as morphologic precursors of common epithelial tumors of ovary. The finding of inclusion cysts and tubal metaplasia in the right ovary of our case may support this hypothesis. The right ovary in our patient showed a prominent stromal vascular pattern, which may be related to the generalized hemangiomatosis seen in MS, noting that our patient had both subcutaneous and visceral hemangiomas. It is not clear whether the ovarian pathology seen in our case was only coincidental or whether it could be attributed to a common embryonic meso-ectodermal developmental dysplasia.16,24 This concept is supported by reports of dysplastic conditions seen in association with enchondromatosis, such as bilateral renal agenesis,25 and the congenital anomalies indicative of Goldenhar’s syndrome (oculoauriculovertebral dysplasia).26

Because of the common tendency for development of neoplasms in patients with enchondromatosis, it is important that these patients are followed carefully, with special emphasis on periodic imaging of abdomen and pelvis for occult neoplasms. Additional studies are needed to understand the pattern of transmission and the proposed embryonic meso-ectodermal developmental dysplasia of enchondromatosis.

*Link no longer available

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D I S E A S E : Enchondromatosis

Synonym(s)
Maffucci syndrome
Ollier disease

Maffucci's syndrome is characterized by the presence of multiple enchondromas and cutaneous hemangiomas. Intracranial chondrosarcomas may be associated with this syndrome. Immunohistochemical studies are necessary to differentiate chondrosarcomas from chordomas. Its etiology is still unclear. Maffucci's syndrome is a dysembryoplasia of the mesoderm, explaining the dual involvement of cartilage and vascular tissue. The risk of malignant degeneration or associated tumors is probably high in this uncommon disease, suggesting that there is an additional oncogenic factor. * Author: S. Aymé, M.D. (June 1999) *

MIM : 166000 

Clnical Signs

   asymmetry of the body (Very frequent sign)
   autosomal dominant inheritance (Very frequent sign)
   bowed diaphysis (Very frequent sign)
   haemangioma-cavernous (Very frequent sign)
   restricted joint mobility (Very frequent sign)
   visceral angiomatosis (Very frequent sign)
   mutiple fractures (Frequent sign)
   neoplasia/cancer (Frequent sign)
   decreased skin pigmentation irregular (Occasional sign)
   lymphoedema/oedema (Occasional sign)

Other Websites

 BoneTumor.org, USA

IInformation for the disease. General public
Site in english

Collège des Enseignants en Radiologie de France

Information for the disease. Public : health professionals
Site in french

Hemangiomas and vascular anomalies, USA

Information for the disease. General public
Site in english

National Organization for Rare Disorders, USA
  
Information for the disease. Information centers repertory. General public
Site in english

Site francophone sur les anomalies vasculaires, Québec

http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=17509&Disease_Disease_Search_diseaseGroup=maffucci-s-syndrome&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Maffucci-syndrome&title=Maffucci-syndrome&search=Disease_Search_Simple

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Maffucci Syndrome

Important

It is possible that the main title of the report Maffucci Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms 

Disorder Subdivisions

General Discussion

Maffucci Syndrome is a rare genetic disorder characterized by benign overgrowths of cartilage (enchondromas), skeletal deformities, and dark red irregularly shaped patches of skin (hemangiomas). Enchondromas are most often found in certain bones (phalanges) of the hands and feet. Skeletal malformations may include legs that are disproportionate in length and/or abnormal side-to-side curvature of the spine (scoliosis). In many cases, bones may tend to fracture easily. In most cases, hemangiomas appear at birth or during early childhood and may be progressive. Maffucci Syndrome is inherited as an autosomal dominant genetic trait.

Resources

National Organization for Rare Disorders, Inc.
55 Kenosia Ave
PO Box 1968
Danbury, CT 06813-1968
Tel: (203)744-0100
Fax: (203)798-2291
Tel: (800)999-6673
TDD: (203)797-9590
Email: orphan@rarediseases.org
Internet: http://www.rarediseases.org

American Cancer Society, Inc.
1599 Clifton Road NE
Atlanta, GA 30329
USA
Tel: 4043203333
Tel: 8002272345
Email: None.
Internet: http://www.cancer.org

NIH/National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse
1 AMS Circle
Bethesda, MD 20892-3675
USA
Tel: 3014954484
Fax: 3017186366
Tel: 8772264267
TDD: 3015652966
Email: niamsinfo@mail.nih.gov
Internet: http://www.niams.nih.gov

NIH/National Heart, Lung and Blood Institute
31 Center Drive MSC 2480
Building 31A Rm 4A16
Bethesda, MD 20892-2480
Tel: (301)592-8573
Fax: (301)480-4907
Email: nhlbiinfo@rover.nhlbi.nih.gov
Internet: http://www.nhlbi.nih.gov/

NIH/Patient Referral Services Unit
Warren Grant Magnuson Clinical Center
Patient Referral and Recruitment Center
Bldg 61
10 Cloister Ct
Bethesda, MD 20892
United States
Tel: 8004111222
Internet: http://www.cc.nih.gov/

Birth Defect Research for Children, Inc.
930 Woodcock Rd
Suite 225
Orlando, FL 32803
USA
Tel: 4078950802
Fax: 4078950824
Email: abcd@birthdefects.org
Internet: http://www.birthdefects.org

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc. ® (NORD). A copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. 

http://www.questdiagnostics.com/kbase/nord/nord433.htm

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A case of Maffucci 's syndrome with pleural effusion: ten-year follow-up.

Biber C, Ergun P, Turay UY, Erdogan Y, Hizel SB.

Ataturk Chest Disease and Surgery Center, Ankara, Turkey. Cigdemdr@yahoo.com

IINTRODUCTION: Maffucci 's syndrome (MS) is a congenital non-hereditary mesodermal dysplasia characterised by numerous mesenchymal neoplasias in the form of enchondromas with secondary bone deformities and multiple soft tissue haemangiomas that may have phlebolitis. CLINICAL PICTURE: A 23-year-old male patient presented with non-productive cough, dyspnoea, chest pain and back pain. Chest X-ray showed unilateral pleural effusion and multiple enchondromas of the ribs. On physical examination, there were mobile, multiple, bluish-coloured lesions probably cavernous haemangiomas on bilateral chest walls. In addition, there were multiple nodular lesions on the extremities especially accumulated on the fingers. The patient was diagnosed as Maffucci 's syndrome according to computed tomography (CT) of the thorax, conventional radiography of the skeletal system, magnetic resonance (MR) imaging, Th4-Th11 intercostal and right upper extremity angiography and physical examination findings. TREATMENT: As the patient rejected any diagnostic intervention, he was monitored with CT. OUTCOME: During the last 6 years of follow-up, the lesion that was detected on the rib adjacent to the basal segments of the left lung showed significant progression and was accepted as chondrosarcoma. CONCLUSION: To our knowledge, this is the first case of Maffucci ' s syndrome with pleural effusion. In this case report, the probable mechanism of pleural effusion was discussed.

Publication Types:

PMID: 15175777 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15175777&itool=iconfft

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Maffucci's syndrome complicated by intracranial chondrosarcoma: two new illustrative cases.

Sept 2007

Dini LI, Isolan GR, Saraiva GA, Dini SA, Gallo P.

Department of Neurosurgery, Hospital Centenário, Avenida Theodomiro Porto da Fonseca 799, 93020-080 São Leopoldo, RS, Brazil. lenadrodini@ig.com.br

Maffucci's syndrome is a rare congenital condition, sometimes misdiagnosed as Ollier's disease, characterized by multiple enchondromas combined with hemangiomas and phlebectasia. Coexisting primary malignancies have been described sporadically. We report two cases of Maffucci's syndrome associated with cranial base chondrosarcoma, emphasizing pathophysiological features and the challenging management of intracranial chondrosarcomas. To the best of our knowledge, only twelve similar cases have been reported in the literature.

SciFlo

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Maffucci's syndrome with giant tumor of the thoracic wall]

[Article in Polish]

Strzalka M, Drozdz W, Kulawik J.

II Katedra Chirurgii Ogolnej Collegium Medicum Uniwersytetu Jagiellonskiego, 31-501 Krakow, ul. Kopernika 21.

Maffucci's syndrome is a rare nonhereditary malformation of mesodremal dysplasia origin which consists of multiple hemangiomas of the soft tissue and multiple enchondromas. Only approximately 170 cases of this disease have been reported in the literature. Maffucci's syndrome is known to be associated with tumors of mesodermal origin. Chondrosarcoma, osteosarcoma and angiosarcoma are the most common malignant neoplasms and the benign tumors consist of pituitary adenoma, adrenal cortical adenoma, parathyroid adenoma, thyroid adenoma and breast fibroadenoma. We present a case report of a 26-year old female patient with Maffucci's syndrome and a giant thorax tumor composed of fibroadenoma and canalicular adenoma.

Publication Types:

PMID: 14679700 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14679700&itool=iconabstr

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Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.

Dec 2004

Rozeman LB, Sangiorgi L, Briaire-de Bruijn IH, Mainil-Varlet P, Bertoni F, Cleton-Jansen AM, Hogendoorn PC, Bovée JV.

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Enchondromatosis (Ollier disease, Maffucci syndrome) is a rare developmental disorder characterized by multiple enchondromas. Not much is known about its molecular genetic background. Recently, an activating mutation in the parathyroid hormone receptor type 1 (PTHR1) gene, c.448C>T (p.R150C), was reported in two of six patients with enchondromatosis. The mutation is thought to result in upregulation of the IHH/PTHrP pathway. This is in contrast to previous studies, showing downregulation of this pathway in other cartilaginous tumors. Therefore, we investigated PTHR1 in enchondromas and chondrosarcomas from 31 enchondromatosis patients from three different European countries, thereby excluding a population bias. PTHR1 protein expression was studied using immunohistochemistry, revealing normal expression. The presence of the described PTHR1 mutation was analyzed, using allele-specific oligonucleotide hybridization confirmed by sequence analysis, in tumors from 26 patients. In addition, 11 patients were screened for other mutations in the PTHR1 gene by sequence analysis. Using both allele-specific oligonucleotide hybridization and sequencing, we could neither confirm the previously found mutation nor find any other mutations in the PTHR1 gene. These results indicate that the PTHR1 gene is not, in contrast to previous suggestions, the culprit for enchondromatosis.

Wiley InterScience

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Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2.

Nov. 2011
Amary MF, Damato S, Halai D, Eskandarpour M, Berisha F, Bonar F, McCarthy S, Fantin VR, Straley KS, Lobo S, Aston W, Green CL, Gale RE, Tirabosco R, Futreal A, Campbell P, Presneau N, Flanagan AM.

Source

Histopathology Unit, Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, UK.

Abstract

Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes.

http://www.nature.com/ng/journal/v43/n12/full/ng.994.html

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Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome.

2011

Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV.

Source

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.

http://www.nature.com/ng/journal/v43/n12/full/ng.1004.html

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Incidence, predictive factors, and prognosis of chondrosarcoma in patients with ollier disease andmaffucci syndrome: an international multicenter study of 161 patients.

2011
Verdegaal SH, Bovée JV, Pansuriya TC, Grimer RJ, Ozger H, Jutte PC, San Julian M, Biau DJ, van der Geest IC, Leithner A, Streitbürger A, Klenke FM, Gouin FG, Campanacci DA, Marec-Berard P, Hogendoorn PC, Brand R, Taminiau AH.

Source

Leiden University Medical Center, Orthopedic Surgery, Postbus 9600/J11-R, Leiden, The Netherlands. shmverdegaal@hotmail.com.

Abstract

Background. Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. Method. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffuccipatients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Results. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). Conclusions. Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.

http://theoncologist.alphamedpress.org/content/16/12/1771.full.pdf+html

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External Links:

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Maffucci syndrome: a genome-wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases. Sept 2011

http://onlinelibrary.wiley.com/doi/10.1002/gcc.20889/abstract

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Hemangioma related to Maffucci syndrome in a man: a case report. Jun 2011

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141690/?tool=pubmed

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Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome. Apr 2011

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077396/?tool=pubmed

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Hand involvement in Ollier Disease and Maffucci Syndrome: a case series. Jul-Sep 2010

http://www.ncbi.nlm.nih.gov/pubmed/20975644

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Chondrosarcoma of the trachea in a patient with Maffucci syndrome. Apr 2010

http://www.deckerpublishing.com/pubMedLinkOut.aspx?pub=JOTOO&vol=39&iss=2&page=E12

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References:
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Enchondroma and Enchondromatosis (1)

Maffucci Syndrome - eMedicine (2)

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Molecular diagnosis of Maffucci Syndrome (PTHR1 gene) 

http://www.genecards.org/cgi-bin/carddisp.pl?gene=PTHR1

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Clasifications and Codes:

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ICD-10

Q78.4 Enchondromatosis
Maffucci's syndrome
Ollier's disease

ICD-9

2012ICD-9-CM Diagnosis 756.4

Chondrodystrophy

  • An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001)
  • Benign growths of cartilage in the metaphyses of several bones.
  • 756.4 is a specific code that can be used to specify a diagnosis
  • 756.4 contains 40 index entries
  • View the ICD-9-CM Volume 1 756.* hierarchy

756.4 also known as:

  • Achondroplasia
  • Chondrodystrophia (fetalis)
  • Dyschondroplasia
  • Enchondromatosis
  • Ollier's disease

756.4 excludes:

  • congenital myotonic chondrodystrophy (359.23)
  • lipochondrodystrophy [Hurler's syndrome] (277.5)
  • Morquio's disease (277.5)

MeSH D004687

eMedicine derm/256 

DiseaseDB 9212 http://www.diseasesdatabase.com/ddb9212.htm

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Lymphedema People - Support Groups

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Children with Lymphedema

The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People.

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Lymphatic Disorders Support Group @ Yahoo Groups

While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.

DISCRIPTION

Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
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Diuretics are not for Lymphedema 

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Lymphedema People Online Support Groups 

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Lymphedema and Pain Management 

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Manual Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)

http://www.lymphedemapeople.com/wiki/doku.php?id=manual_lymphatic_drainage_mld_complex_decongestive_therapy_cdt 

Infections Associated with Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema 

How to Treat a Lymphedema Wound 

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound 

Fungal Infections Associated with Lymphe dema 

http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema 

Lymphedema in Children 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children 

Lymphoscintigraphy 

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Magnetic Resonance Imaging 

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Extraperitoneal para-aortic lymph node dissection (EPLND) 

http://www.lymphedemapeople.com/wiki/doku.php?id=extraperitoneal_para-aortic_lymph_node_dissection_eplnd 

Axillary node biopsy 

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Sentinel Node Biopsy 

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Small Needle Biopsy - Fine Needle Aspiration 

http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy 

Magnetic Resonance Imaging 

http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging 

Lymphedema Gene FOXC2

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2

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http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc

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 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18

 Lymphedema and Pregnancy

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Home page: Lymphedema People

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Page Updated: Jan. 5, 2012