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Orthopedic Research and Reviews 2019Hereditary multiple exostoses (HME), also called hereditary multiple osteochondromas, is a rare genetic disorder characterized by multiple osteochondromas that grow near... (Review)
Review
Hereditary multiple exostoses (HME), also called hereditary multiple osteochondromas, is a rare genetic disorder characterized by multiple osteochondromas that grow near the growth plates of bones such as the ribs, pelvis, vertebrae and especially long bones. The disease presents with various clinical manifestations including chronic pain syndromes, restricted range of motion, limb deformity, short stature, scoliosis and neurovascular alteration. Malignant transformation of exostosis is rarely seen. The disease has no medical treatment and surgery is only recommended in symptomatic exostoses or in cases where a malignant transformation is suspected. HME is mainly caused by mutations and functional loss of the EXT1 and EXT2 genes which encode glycosyltransferases, an enzyme family involved in heparan sulfate (HS) synthesis. However, the peculiar molecular mechanism that leads to the structural changes of the cartilage and to osteochondroma formation is still being studied. Basic science studies have recently shown new insights about altering the molecular and cellular mechanism caused by HS deficiency. Pediatricians, geneticists and orthopedic surgeons play an important role in the study and treatment of this severe pathology. Despite the recent significant advances, we still need novel insights to better specify the role of HS in signal transduction. The purpose of this review was to analyze the most relevant aspects of HME from the literature review, give readers an important tool to understand its clinical features and metabolic-pathogenetic mechanism, and to identify an effective treatment method. We focused on the aspects of the disease related to clinical management and surgical treatment in order to give up-to-date information that could be useful for following best clinical practice.
PubMed: 31853203
DOI: 10.2147/ORR.S183979 -
Frontiers in Genetics 2021Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized... (Review)
Review
Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized by multiple benign cartilage-capped bony outgrowths, termed exostoses or osteochondromas, that locate most commonly in the juxta-epiphyseal portions of long bones. Affected individuals usually complain of persistent pain caused by the pressure on neighboring tissues, disturbance of blood circulation, or rarely by spinal cord compression. However, the most severe complication of this condition is malignant transformation into chondrosarcoma, occurring in up to 3.9% of HMEs patients. The disease results mainly from heterozygous loss-of-function alterations in the or genes, encoding Golgi-associated glycosyltransferases, responsible for heparan sulfate biosynthesis. Some of the patients with HMEs do not carry pathogenic variants in those genes, hence the presence of somatic mutations, deep intronic variants, or another genes/loci is suggested. This review presents the systematic analysis of current cellular and molecular concepts of HMEs along with clinical characteristics, clinical and molecular diagnostic methods, differential diagnosis, and potential treatment options.
PubMed: 34956317
DOI: 10.3389/fgene.2021.759129 -
Clinical Cases in Mineral and Bone... 2016Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare... (Review)
Review
Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology.
PubMed: 27920806
DOI: 10.11138/ccmbm/2016.13.2.110 -
Frontiers in Genetics 2021Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans,... (Review)
Review
Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.
PubMed: 34539746
DOI: 10.3389/fgene.2021.717535 -
Danish Medical Journal Sep 2014Hereditary multiple cartilaginous exostoses is a syndrome characterised by the development of multiple osteochondromas. The diagnosis is typically made around the age of... (Review)
Review
INTRODUCTION
Hereditary multiple cartilaginous exostoses is a syndrome characterised by the development of multiple osteochondromas. The diagnosis is typically made around the age of 12 years, and the prevalence is estimated at 1:50,000. During skeletal growth, the osteochondromas are benign, but in adult life malignant transformation into chondrosarcomas can occur.
METHODS
This study was a literature survey based on a systematic search of the PubMed database for articles with the term "hereditary multiple exostoses chondrosarcoma". The search returned 157 articles, of which 13 had a sufficient level of evidence. These publications were examined thoroughly, focusing on the development of sarcomas, symptoms and the risk of malignant degeneration.
RESULTS
There is no consensus regarding the frequency of malignant transformation of multiple cartilaginous exostoses into sarcomas, which varies from less than 1% to 25%. The most reliable estimation seems to be 1-2%. The survey of the literature shows that no risk groups can be identified. However, exostoses in the axial skeleton are more prone to develop into chondrosarcomas than peripheral exostoses.
CONCLUSION
It is indisputable that malignant transformation occurs, and we therefore propose that a follow-up programme be launched with clinical examination by magnetic resonance imaging or bone scintigraphy every second year. The purpose of such programme would be to discover the sarcomatous development as early as possible to improve the survival prognosis of the patients. This screening programme should be centralised at tumour departments.
Topics: Bone Neoplasms; Cell Transformation, Neoplastic; Chondrosarcoma; Early Detection of Cancer; Exostoses, Multiple Hereditary; Humans; Precancerous Conditions
PubMed: 25186537
DOI: No ID Found -
Current Osteoporosis Reports Jun 2017Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal... (Review)
Review
PURPOSE OF REVIEW
Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs, and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically based therapeutic intervention.
RECENT FINDINGS
Most HME cases are linked to loss-of-function mutations in EXT1 or EXT2 that encode glycosyltransferases responsible for heparan sulfate (HS) synthesis, leading to HS deficiency. Recent genomic inquiries have extended those findings but have yet to provide a definitive genotype-phenotype correlation. Clinical studies emphasize that in addition to the well-known skeletal problems caused by osteochondromas, HME patients can experience, and suffer from, other symptoms and health complications such as chronic pain and nerve impingement. Laboratory work has produced novel insights into alterations in cellular and molecular mechanisms instigated by HS deficiency and subtending onset and growth of osteochondroma and how such changes could be targeted toward therapeutic ends. HME is a rare and orphan disease and, as such, is being studied only by a handful of clinical and basic investigators. Despite this limitation, significant advances have been made in the last few years, and the future bodes well for deciphering more thoroughly its pathogenesis and, in turn, identifying the most effective treatment for osteochondroma prevention.
Topics: Chronic Pain; Exostoses, Multiple Hereditary; Humans; Mutation; N-Acetylglucosaminyltransferases; Nerve Compression Syndromes
PubMed: 28466453
DOI: 10.1007/s11914-017-0355-2 -
Journal of Children's Orthopaedics Dec 2016The risk and consequences of an elbow or a wrist contracture are lower during a forearm lengthening than during a lower limb lengthening. This kind of complication can... (Review)
Review
The risk and consequences of an elbow or a wrist contracture are lower during a forearm lengthening than during a lower limb lengthening. This kind of complication can mostly be avoided by an active and intensive regimen of physiotherapy. However, there are some challenges to deal with in treating the disorder multiple exostoses and the radial club hand, including the lack of consensus on the best treatment for multiple exostoses. However, it is important to realize that the evolution of multiple exostoses can lead to a radial head dislocation which will damage the pronation and the supination range of motion. As this motion can be poor even without a radial head dislocation as a result of the radius being longer than the ulna, an interesting technique can be to lengthen the ulna to limit this phenomenon. In radial club hand, the main problem is the deviation of the hand requiring a centralization. The best treatment for centralization of the hand is to do a progressive correction with an external fixator. Thereafter, it is possible to lengthen the forearm, but this indication is mainly cosmetic in the unilateral radial club hand.
PubMed: 27826904
DOI: 10.1007/s11832-016-0786-9 -
Spinal Cord Series and Cases May 2020Osteochondromas are benign bone tumors which occur as solitary lesions or as part of the syndrome multiple hereditary exostoses. While most osteochondromas occur in the...
INTRODUCTION
Osteochondromas are benign bone tumors which occur as solitary lesions or as part of the syndrome multiple hereditary exostoses. While most osteochondromas occur in the appendicular skeleton, they can also occur in the spine. Most lesions are asymptomatic however some may encroach on the spinal cord or the nerve roots causing neurological symptoms. While most patients with osteochondromas undergo laminectomy without fusion, laminectomy with fusion is indicated in appropriately selected cases of spinal decompression.
CASE PRESENTATION
We present a case of a 32-year-old male with history of multiple hereditary exostoses who presented with symptoms of bilateral upper extremity numbness and complaints of gait imbalance and multiple falls. He reported rapid progression of his symptoms during the 10 days before presentation. Computed tomography of the cervical spine revealed a lobulated bony tumor along the inner margin of the cervical 4 lamina. He underwent cervical 3 and 4 laminectomies, partial cervical 2 and 5 laminectomies and cervical 3-5 mass screw placement. Pathology was consistent with osteochondroma. The patient's symptoms had markedly improved at follow-up.
CONCLUSION
According to our literature review, osteochondromas most commonly occur at cervical 2 and cervical 5. We present a case of an osteochondroma at a less common level, cervical 4. While most osteochondromas are addressed with laminectomy without arthrodesis, the decision of whether arthrodesis is necessary should be considered in all patients with osteochondroma as with any cervical decompression.
Topics: Adult; Arthrodesis; Cervical Vertebrae; Clinical Decision-Making; Humans; Male; Osteochondroma; Spinal Neoplasms
PubMed: 32467563
DOI: 10.1038/s41394-020-0292-7 -
SAGE Open Medical Case Reports 2022Osteochondroma is the most common bone tumor representing 20%-50% of all benign bone tumors and 10%-15% of all bone tumors. Osteochondroma has similar radiological...
Osteochondroma is the most common bone tumor representing 20%-50% of all benign bone tumors and 10%-15% of all bone tumors. Osteochondroma has similar radiological appearance in both solitary and multiple forms; the latter is an autosomal dominant disorder termed hereditary multiple exostoses. Associated complications of osteochondroma include deformity, fracture, neurovascular compromise, bursa formation, and malignant transformation. Measurement of the cartilage cap thickness is an important index suggesting secondary malignancy of osteochondroma. The upper limit of cap thickness after skeletal maturation is 1.5 cm which can be reliably measured on ultrasound or magnetic resonance imaging. Hereditary multiple exostoses are linked to the mutations of different exostoses genes located on chromosome 8, 11, and 19. We reported cases of two siblings presented with multiple osteochondromas managed by surgical excision. We evaluated their clinical and radiological presentation, genetic correlations and compared with the literature.
PubMed: 35693925
DOI: 10.1177/2050313X221103732