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Background Hereditary multiple exostoses (HME) is a rare skeletal disorder characterised by a widespread. distribution of osteochondromas originating from the metaphyses of long bones. Case presentation This case study examines a 55-year-old male cadaver bequeathed to the University of Liverpool who suffered from HME, thus providing an exceptionally rare opportunity to examine the anatomical changes associated with this condition. Conclusions Findings from imaging and dissection indicated that this was a severe case of HME in terms of the quantity and distribution of the osteochondromas and the number of synostoses present. In addition, the existence of enchondromas and the appearance of gaps within the trabeculae of affected bones make this a remarkable case. This study provides a comprehensive overview of the morbidity of the disease as well as adding to the growing evidence that diseases concerning benign cartilaginous tumours may be part of a spectrum rather than distinct entities.

Metachondromatosis is a rare disorder of autosomal inheritance with incomplete penetrance, which is characterized by formation of osteochondroma and enchondroma, caused by loss of function of the protein tyrosine phosphatase nonreceptor type 11 (PTPN11) gene. Diagnosis is made based on the distribution and orientation of lesions with history of regression of lesions with time and confirmed by genetic mutation of PTPN11 gene. We report a rare case of a 24-year-old male with Alport's syndrome with metachondromatosis due to missense variation in PTPN11 gene.

Ollier disease and Maffucci syndrome are the commonest enchondromatosis subtypes, arising from non-hereditary mutations in the IDH1 and IDH2 genes, presenting in childhood and being characterised by multiple enchondromas. Maffucci syndrome also includes multiple soft tissue haemangiomas. Aside from developing bony masses, osseous deformity and pathological fracture, ~ 40% of these patients develop secondary central chondrosarcoma, and there is increased risk of non-skeletal malignancies such as gliomas and mesenchymal ovarian tumours. In this review, we outline the molecular genetics, pathology and multimodality imaging features of solitary enchondroma, Ollier disease and Maffucci syndrome, along with their associated skeletal complications, in particular secondary chondrosarcoma. Given the lifelong risk of malignancy, imaging follow-up will also be explored. Metachondromatosis, a rare enchondromatosis subtype characterised by enchondromas and exostoses, will also be briefly outlined.

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial, ear, branchial, and musculoskeletal anomalies, along with hearing loss and mild intellectual disability. Clinically, its distinction from branchiootorenal syndrome can be difficult. To date, the coexistence of OFCS and metachondromatosis has not been reported. Here, we describe a sporadic patient with both OFCS and metachondromatosis. This novel association prompts us to do some remarks on the clinical variability of branchial-arch disorders; in fact, our observations are consistent with the highly variable expressivity of OFCS and illustrate the need of a more accurate characterization of these branchial-arch disorders. In the meantime, involvement of clavicles, scapulae and shoulders remains a distinctive feature of OFCS.

Rationale Metachondromatosis (MC) is a very rare genetic disease, which is infrequently reported worldwide, which leads to osteochondroma and enchondromatosis. The disease has been shown to be associated with loss of function of the tumor suppressor gene "protein tyrosine phosphatase, non-receptor type 11" (PTPN11). Patient concerns A 12-year-old female was admitted to the hospital with pain due to an enlarged mass in her left fifth finger. Diagnosis Examination of the left hand by computed tomography (CT) revealed an expanding type of round and low-density lesion in the fifth proximal phalanx. The patient then underwent technetium-99m methylene diphosphonate single-photon emission CT/CT (Tc-MDP SPECT/CT) to assess the nature of the lesion. The SPECT/CT image revealed dilated osteopathy and increased activity of the fifth proximal phalanx on the left hand. Unexpectedly, the examination of the right hand revealed slight expanded lesions and increased activities of the third metacarpal and proximal phalange, as well as the fourth proximal phalange and the middle phalanx. On the basis of the patient's symptoms and the results of the above-mentioned examinations, we diagnosed the patient as having MC in her hands. Intervention Considering the pain of the fifth finger of the left hand, the patient underwent debridement of the fifth proximal phalanx of the left hand and internal fixation with bone graft taken from the body. Outcomes The patient was discharged after a week of observation. One year later, she was admitted to the hospital again for removal of the bone healing internal fixation after osteoma surgery. Preoperative Tc-MDP SPECT/CT revealed that the left-handed lesions displayed postoperative changes, while the multiple lesions in the right hand increased in volume but remained unchanged in number. Lessons This case revealed the CT and Tc-MDP SPECT/CT imaging features of MC. Specifically, SPECT/CT imaging contributed to the diagnosis of clinically asymptomatic bone lesions, and the 3D SPECT/CT fusion allowed a more comprehensive and intuitive view of the lesion by combining anatomy and function.

Background: The autosomal dominant condition multiple osteochondromas, formerly called multiple hereditary exostoses, is associated with a risk of malignant progression of osteochondroma into secondary peripheral chondrosarcoma. Most patients with multiple osteochondromas have exostosin-1 or exostosin-2 gene mutations. To our knowledge, it has not been previously reported that patients may also harbor intraosseous (central) chondroid neoplasms, enchondromas, or atypical chondroid tumors or central chondrosarcomas. The combination of osteochondroma and enchondromas also exists in patients with metachondromatosis, a disorder associated with a protein tyrosine phosphatase non-receptor type 11 gene mutation. This study aims to establish any correlation between multiple osteochondromas and intraosseous cartilaginous neoplasms. Methods: We retrospectively reviewed all histologically proven intraosseous atypical chondroid tumors or chondrosarcomas in our prospective nationwide Dutch tertiary referral multiple osteochondromas database. Demographic, clinical, radiographic, histological, and genetic data were recorded. The institutional medical ethics review board approved the study. Results: From 195 adult patients, seven (3.6%) were identified with intraosseous atypical chondroid tumor or chondrosarcoma World Health Organization grade 1 and had a mean age of forty-two years; five of these patients were male. In all cases, radiographic and genetic findings were consistent with multiple osteochondromas, not metachondromatosis; three patients had an exostosin-1 mutation, four patients had an exostosin-2 mutation, and no patients had a protein tyrosine phosphatase, non-receptor type 11 mutation. Six patients underwent successful operative treatment without complications or recurrences after a mean follow-up duration of forty-eight months (range, twelve to 144 months). One patient was scheduled for surgery after biopsy and histologic confirmation. Of the seven patients, five (71%) also developed a peripheral chondrosarcoma in a known osteochondroma during the study period. Conclusions: Apart from osteochondromas or peripheral chondrosarcomas, multiple osteochondromas are also associated with intraosseous chondroid neoplasms, potentially resulting in central chondrosarcoma. Therefore, intraosseous lesions should not automatically be regarded as innocuous in this patient population. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Four members of a family – three of whom have facial features mildly resembling those of the trichorhinophalangeal syndrome, type I, and all of whom manifested appendicular bony prominences similar to trichorhinophalangeal syndrome, type II – were found to have the radiographic findings of metachondromatosis. The radiographic manifestations and evolution of metachondromatosis are depicted in this report.

Recently, loss-of-function mutations in PTPN11 were linked to the cartilage tumor syndrome metachondromatosis (MC), a rare inherited disorder featuring osteochondromas, endochondromas and skeletal deformation. However, the underlying molecular and cellular mechanism for MC remained incompletely understood. By studying the role of the Src homology-2 domain-containing protein tyrosine phosphatase Shp2 (encoded by mouse Ptpn11) in cathepsin K-expressing cells, we identified a novel cell population in the perichondrial groove of Ranvier. In the absence of Shp2, these cells exhibit elevated Indian hedgehog (Ihh) signaling, proliferate excessively and cause ectopic cartilage formation and tumors. Our findings establish a critical role for a protein-tyrosine phosphatase (PTP) family member, in addition to the well-known roles of receptor tyrosine kinases (RTKs), in cartilage development and homeostasis. However, whether Shp2 deficiency in other epiphyseal chondroid cells and whether signaling pathways in addition to the IHH/Parathyroid Hormone-related Peptide (PTHrP) axis attribute to the formation of enchondromas and osteochondromas remains elusive. Understanding how chondrogenic events are regulated by SHP2 could aid in the development of novel therapeutic approaches to prevent and treat cartilage diseases, such as MC and osteoarthritis (OA).

Introduction Metachondromatosis is a rare genetic disease of osteochondroma and enchondroma formation, caused by loss of function of the PTPN11 gene. It is distinct from other similar conditions such as multiple osteochondromas and hereditary multiple exostoses by the distribution and orientation of lesions, and pattern of inheritance. Lesions typically occur in hands, feet, femora, tibiae and the pelvis. Lesions are typically reported to regress in adulthood. Methods We reviewed the current literature on metachondromatosis, and present four new cases in a family with metachondromatosis. Results Long-term follow up data reveal spontaneous regression of lesions by skeletal maturity. Complications may include nerve palsy due to the mass effect of lesions, avascular necrosis of the femoral head and angular deformity of long bones. Histopathological analysis has demonstrated that lesions in metachondromatosis are a mix of osteochondromas and enchondromas; however, one case of chondrosarcoma has been reported. Conclusion Lesions associated with metachondromatosis may cause a variety of complications due to mass effects; however, they are often asymptomatic, cause cosmetic concerns and, importantly, most regress spontaneously. Regular clinical review with selective imaging to monitor for such complications is appropriate, but uncomplicated lesions are unlikely to require surgical intervention.

The disorders discussed here reflect localized disturbances of the endochondral growth plate development or localized disturbances of bone maturation. In the first category are dysplasia epiphysealis hemimelica, hereditary multiple exostoses and its variant Langer–Giedion syndrome, and enchondromatosis and its variants Maffucci syndrome and metachondromatosis. They are due to asymmetrical, displaced, or aberrant growth of endochondral cartilage tissues that interferes with normal skeletal development, and which may occur as an isolated finding or in concert with other disease manifestations. Some conditions are inherited, but others occur sporadically. The second category comprises fibrous dysplasia of bone, which can be monostotic or polyostotic as an element of McCune–Albright syndrome, and cherubism. Fibrous dysplasia results from somatic activating mutations of GNAS1 , which produce McCune–Albright syndrome if they occur early in development or isolated bone lesions if they occur later. Cherubism, which is characterized by painless symmetrical swelling of the jaws during childhood, results from heterozygous mutations of the adapter protein SH3BP2.

The disorders discussed here reflect localized disturbances of the endochondral growth plate development or localized disturbances of bone maturation. In the first category are dysplasia epiphysealis hemimelica, hereditary multiple exostoses and its variant Langer–Giedion syndrome, and enchondromatosis and its variants Maffucci syndrome and metachondromatosis. They are due to asymmetrical, displaced, or aberrant growth of endochondral cartilage tissues that interferes with normal skeletal development and which may occur as an isolated finding or in concert with other disease manifestations. Some conditions are inherited, but others occur sporadically. The second category comprises fibrous dysplasia of bone, which can be monostotic or polyostotic as an element of McCune–Albright syndrome, and cherubism. Fibrous dysplasia results from somatic activating mutations of GNAS1, which produce McCune–Albright syndrome if they occur early in development or isolated bone lesions if they occur later. Cherubism, which is characterized by painless symmetrical swelling of the jaws during childhood, results from heterozygous mutations of the adaptor protein SH3BP2.

Case: A nine-year-old boy had multiple osteochondromas in the hands, feet, and tibiae, many of which pointed toward the adjacent joint. Although several were treated surgically, others resolved spontaneously. A heterozygous mutation in the PTPN11 gene was identified by genetic analysis of peripheral blood, so the patient was diagnosed with metachondromatosis despite the absence of enchondromatous lesions. Conclusion: To the best of our knowledge, this is the first reported case of a patient with metachondromatosis without any enchondromatous lesions.

Metachondromatosis (MC) and hereditary multiple osteochondromas (HMO) are thought to be distinct disorders, each with characteristic x-ray and clinical features. Radiographic differences are the current mainstay of differential diagnosis. Both disorders are autosomal dominant, but the majority of patients with HMO have mutations in EXT-1 or EXT 2 genes. The genetic defect in MC is unknown, although recent studies indicate a possible identifiable mutation. The cancer risk in HMO is thought to be greater than in MC, although the small number of cases make such conjecture imprecise. The purpose of this report is to review existing literature and examine whether radiographic findings in HMO and MC can be reliable as a stand-alone means of differential diagnosis. Three members of a multi-generational family with an autosomal dominant exostosis syndrome were studied by clinical examination and complete skeletal survey. The roentgenographic characteristics of all osteochondromas were analyzed. The father underwent gene sequencing for EXT-1 and EXT-2, which revealed a novel EXT-2 mutation. Typical radiographic and clinical findings of both HMO and MC were seen throughout the family as well as in individuals. These family study findings contradict many of the long-standing clinical and x-ray diagnostic criteria for differentiating MC from HMO. The phenotypic crossover between the two conditions in this family, and results of genetic analysis, suggest that in the absence of a definitive genetic diagnosis, radiographic and clinical diagnosis of past and future cases HMO and MC may not be as reliable as previously assumed.

Metachondromatosis is a rare, inherited disease that was described in 1971 by Maroteaux1. He chose the name metachondromatosis to emphasize the evolving or changing nature of the chondromatous lesions1-5. The complete form of the disease is characterized by multiple metaphyseal juxtaepiphyseal exostoses, metaphyseal enchondromas, periarticular calcifications, and frequent unilateral or bilateral Legg-Calve-Perthes-like changes in the femoral head, resembling osteonecrosis1-3,6-8. The metachondromatosis-associated exostoses are true osteochondromas with cartilaginous caps and characteristically point toward the adjacent joint, often involve the bones of the hands and feet, and do not produce shortening or growth disturbance of the affected bone8. The periarticular calcifications are due to peripheral enchondral ossification in epiphysis-based exophytic enchondromas. The enchondromatous lesions, unlike those of multiple enchondromatosis, most often affect the iliac crests and the metaphyses of certain long bones, showing similar radiographic irregularities. Metachondromatosis-associated enchondromas may appear as metaphyseal enchondromas6,9, have a periarticular flowery appearance3,6,9, or be similar to lesions seen in lytic metastatic disease3,8. The reported locations of these lesions include the iliac crest, proximal and distal end of the femur, proximal part of the fibula, distal end of the tibia, distal aspect of the radius, proximal part of the humerus, and hands and feet4,6,8,9. The disorder has not been mapped in the human genome. The mode of inheritance is autosomal dominant1-3,6,8. Clinical features of metachondromatosis include firm, nontender nodules adjacent to joints in the hands and feet, less frequently at the site of large joints, appearing during the first decade of life6. A common complication is nerve compression that …

We report the case histories, radiographic and computed tomographic studies, and histologic findings of two children with metachondromatosis who developed avascular necrosis (AVN) of the femoral ossific nucleus. The first was a 9-year-old boy with involvement of both femoral heads; the second was an 8-year-old girl with involvement of her right femoral head. The changes were associated with either exostoses or enchondromalike lesions of the femoral neck. Interference with the integrity of the lateral epiphyseal vessels by these lesions would explain the avascular changes that occurred. The findings in these cases and other reports associating AVN with skeletal dysplasia should encourage treating physicians to analyze carefully a sudden increase in hip pain or rapid radiographic development of femoral head collapse in a child with a skeletal dysplasia. Recognition of true AVN, in contrast to the gradual evolution of head shape change in typical skeletal dysplasia, may change treatment recommendations and prognosis.

Background Enchondromatosis represent a heterogenous group of disorders. Spranger et al attempted a classification into 6 types: Ollier disease, Maffuci syndrome, metachondromatosis, spondyloenchondrodysplasia, enchondromatosis with irregular vertebral lesions, and generalized enchondromatosis. Halal and Azouz added 3 tentative categories to the 6 in the classification of Spranger et al. Case presentation We report on a 15-year-old boy with acrofrom upper limbs and mixed appearance of radiolucency, cysts and striae of fibro-chondromatosis. Lower limbs (femoral, tibial and fibular dysplasia showed enlarged metaphyses near the knees bilaterally) were present. Additional features of short stature, macrocephaly, facial dysmorphism, and generalised platyspondyly have been encountered. These bone shortenings were associated with bone bending, curving and rhizomelia of the upper limbs with significant macrodactyly. Limitations in articular movements were present. The forearm deformities were similar to those observed in hereditary multiple exostosis. Conclusion The acrofrom upper limbs with mixed appearances of radiolucencies, cysts and striae of fibro-chondromatosis are the basic features of type I1Spranger. The constellation of facial dysmorphic features and significant vertebral abnormalities in our present patient were not compatible with the above-mentioned type of enchondromatosis. Our report widens the knowledge of disorders characterised by enchondromatosis. Ascertainment of the mode of inheritance in our present patient was difficult because of insufficient family history and parents declined clinical/radiographic documentation.

A 6-year-old boy with metachondromatosis, an inherited disorder characterized by multiple enchondromas and exostoses, developed avascular necrosis of the capital femoral epiphysis mimicking Perthes disease. Despite containment, significant coxa magna occurred with flattening and lateral extrusion, requiring intertrochanteric osteotomy and shelf augmentation.

Enchondromas are common intraosseous usually benign cartilaginous tumors that develop in close proximity to growth plate cartilage. Genochondromatosis is a familial skeletal condition with autosomal dominant inheritance pattern. Genochondromatosis type I is a skeletal disorder characterized by symmetrical chondromatosis with characteristic localization: clavicle, upper end of humerus, and lower end of femur. The condition shows a benign course and is clearly different from metachondromatosis, generalized enchondromatosis, and spondyloenchondrodysplasia. In contrast, genochondromatosis type II is characterized by normal clavicles, but metaphyseal involvement of the hands, feet, knees, and wrists. To date, one family has been described with two affected individuals and possibly a second one with seven affected individuals. We report here on a boy with radiographic features of genochondromatosis type II. This report confirms that this disorder represents a separate clinical entity distinguishable for genochondromatosis type I. In addition, this report confirms the benign course of this rare disorder and will help accurate genetic counseling.

Multiple osteochondromas, formerly called multiple hereditary exostoses, is an autosomal dominant heterogeneous disorder that occurs in 1 in 50,000 births1 and is associated with mutations of the exostosin-1 ( EXT1 ) and exostosin-2 ( EXT2 ) genes. Both genes are putative tumor suppressors that encode glycosyltransferases, also known as exostosins, involved in the biosynthesis of heparin sulfate. Penetrance is very high: 96% in female patients and 100% in male patients. In 10% of affected individuals, hereditary multiple osteochondromas is the result of a new mutation2. Clinical manifestations of this disease result in exostoses that generally involve the long bones and result in varying degrees of skeletal deformity and growth disturbances. Malignant transformation, chondrosarcoma that arises in the cartilage cap, occurs in 5% of patients with multiple osteochondromas. Although certain risk and protective factors such as sex, number of lesions, the presence of EXT2 mutations, and the absence of EXT1 or EXT2 correlate with clinical disease severity, none predict malignant transformation3. In the article by Goud and colleagues, the observation that central chondroid tumors are associated with multiple osteochondromas is surprising, as, to my knowledge, it has not been previously reported. Central chondroid tumors, enchondromas, occur in association with exostoses in patients with metachondromatosis, a rare disease that generally affects the hands and feet and is not associated with growth disturbances. Unlike multiple osteochondromas, metachondromatosis is not associated with EXT1 or EXT2 mutations. Although peripheral chondrosarcomas are not uncommon …

If we exclude fibrous structures such as non-ossifying fibroma and cortico-metaphyseal detect, the exostosis is the commonest of benign tumours: 40% of the total according to Dahlin and 10% of all tumours of bone.

Multiple cartilaginous exostoses were diagnosed in a two-year-old Great Dane and a four-month-old border collie. Clinically, the Great Dane showed only mild discomfort, while the border collie exhibited tetraparesis due to cervicothoracic compression. Unusual features in the Great Dane were exostoses that bridged physes, with progression after skeletal maturity. The border collie puppy's exostoses resembled tumoral calcinosis radiographically. Limb exostoses in this puppy often were para-articular, and most were not attached to the underlying bone. These features resembled metachondromatosis in humans. Analysis of previously reported cases of multiple cartilaginous exostoses indicated that the prognosis is guarded to poor.

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Metachondromatosis. Report of four cases. G Bassett;H Cowell; The Journal of Bone & Joint Surgery

2 brothers with possible homozygous multiple cartilaginous exostosis (MCE) are reported. The MCE-PD-(Peripheral Dysostosis) syndrome is discussed. A family (father, daughter and son) with Metachondromatosis is presented, and the tendency to spontaneous remission in this condition is emphasized. A “second thought”, when considering the diagnosis of MCE, seems worthwhile.

Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.