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Cureus Jul 2021Hereditary multiple exostoses (HME) are an autosomal dominant skeletal disorder characterized by the development of multiple benign osteochondromas (exostoses) that... (Review)
Review
Hereditary multiple exostoses (HME) are an autosomal dominant skeletal disorder characterized by the development of multiple benign osteochondromas (exostoses) that frequently involve long bones of the body. Less commonly, the ribs are a site of involvement, and long-term friction between an exostosis and pleura can produce a hemothorax or pneumothorax. The purpose of this study is to provide a comprehensive review of existing literature on pneumothorax or hemothorax secondary to costal exostosis in HME patients. We reviewed the databases of PubMed and Embase and included data as current as of February 15, 2021. All case reports included cases of hemothorax or pneumothorax in patients with a known personal or family history of HME. After evaluation for inclusion based on eligibility criteria, 18 cases were included. The average age at presentation was 11.7 years (range: 3-32), and most patients were male (83%). Hemothoraces occurred in 15 cases, while pneumothoraces occurred in three cases. All cases were evaluated using chest X-ray and CT scan, and the majority of the cases were treated with surgical resection of the exostosis, either with video-assisted thoracoscopic surgery (VATS; 61%) or thoracotomy (22%). Outcomes were successful with no cases of recurrence after surgical intervention. Although rare, costal exostosis should be considered as a differential in patients presenting with pneumothorax or hemothorax and past medical history or physical exam findings suggestive of HME. Immediate evaluation and surgical intervention to resect costal exostosis are essential to reduce the risk of recurrent life-threatening injury.
PubMed: 34395113
DOI: 10.7759/cureus.16326 -
Developmental Dynamics : An Official... Sep 2013Heparan sulfate (HS) is an essential component of cell surface and matrix-associated proteoglycans. Due to their sulfation patterns, the HS chains interact with numerous... (Review)
Review
Heparan sulfate (HS) is an essential component of cell surface and matrix-associated proteoglycans. Due to their sulfation patterns, the HS chains interact with numerous signaling proteins and regulate their distribution and activity on target cells. Many of these proteins, including bone morphogenetic protein family members, are expressed in the growth plate of developing skeletal elements, and several skeletal phenotypes are caused by mutations in those proteins as well as in HS-synthesizing and modifying enzymes. The disease we discuss here is hereditary multiple exostoses (HME), a disorder caused by mutations in HS synthesizing enzymes EXT1 and EXT2, leading to HS deficiency. The exostoses are benign cartilaginous-bony outgrowths, form next to growth plates, can cause growth retardation and deformities, chronic pain and impaired motion, and progress to malignancy in 2-5% of patients. We describe recent advancements on HME pathogenesis and exostosis formation deriving from studies that have determined distribution, activities and roles of signaling proteins in wild-type and HS-deficient cells and tissues. Aberrant distribution of signaling factors combined with aberrant responsiveness of target cells to those same factors appear to be a major culprit in exostosis formation. Insights from these studies suggest plausible and cogent ideas about how HME could be treated in the future.
Topics: Animals; Bone and Bones; Exostoses, Multiple Hereditary; Heparitin Sulfate; Humans; Musculoskeletal Development; N-Acetylglucosaminyltransferases
PubMed: 23821404
DOI: 10.1002/dvdy.24010 -
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 -
Orphanet Journal of Rare Diseases Feb 2008Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is... (Review)
Review
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.
Topics: Adult; Animals; Bone Neoplasms; Cell Transformation, Neoplastic; Child; Chondrosarcoma; Diagnosis, Differential; Exostoses, Multiple Hereditary; Female; Genetic Counseling; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Prognosis; Sex Factors
PubMed: 18271966
DOI: 10.1186/1750-1172-3-3 -
Molecular Medicine Reports Apr 2022The aim of the present study was to report a clinical survey of hereditary multiple exostoses (HME) in a large Chinese pedigree, and the identification of a novel...
The aim of the present study was to report a clinical survey of hereditary multiple exostoses (HME) in a large Chinese pedigree, and the identification of a novel deletion mutation of exostosin glycosyltransferase 2 () gene. A patient with multiple exostoses with huge cartilage‑capped tumors in scapula, knees and ankles received surgery in Department of Orthopedics (Shanghai Changhai Hospital). A total of 20 family members were recruited to the study, with seven members (five male; two female) diagnosed as HME. The family members of the patients with HME were examined, clinical data and peripheral blood samples were collected, and their DNA was sequenced. The incidence of HME in this family pedigree was 35%. Exostoses were most frequently in the tibiae with occurrence in six patients, followed by ribs, femurs, radii, fibulae, scapulae and humeri. DNA sequencing of peripheral blood revealed a novel deletion mutation, c.824‑826delGCA, in exon 5 of the gene, which was observed in all the patients with HME, but not in the healthy family members. Several characteristics of HME in the pedigree were observed, such as susceptibility of male gender, decreased average age of onset and height and increased severity of clinical symptoms with generations.
Topics: China; Exostoses, Multiple Hereditary; Female; Gene Deletion; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Pedigree
PubMed: 35211766
DOI: 10.3892/mmr.2022.12657 -
Clinical Orthopaedics and Related... Apr 2014Subungual exostosis is a relatively common benign bone tumor that occurs in the distal phalanges of the toes and can be a source of pain and nail deformity. There is... (Review)
Review
BACKGROUND
Subungual exostosis is a relatively common benign bone tumor that occurs in the distal phalanges of the toes and can be a source of pain and nail deformity. There is controversy about the treatment of these lesions and there are few studies that have synthesized what is known and provided meaningful information on treatment.
QUESTIONS/PURPOSES
We performed a systematic review to address the following questions: (1) What is the best surgical approach for excising these lesions? (2) What is the age range, sex distribution, and presenting symptoms of subungual exostoses and which toe is most frequently affected? (3) What complications arise from treatment?
METHODS
Two authors independently searched multiple databases (Medline, 1950-May 2013; Cochrane EBM database, and EMBASE, 1980-May 2013 provided by OVID; ACP Journal Club, 2003-May 2013; CINAHL by EBSCO, 1937-May 2013; and PubMed by NLM, 1940-May 2013), and key words were chosen to achieve a broad search strategy. We included studies on the management of toe exostoses with > 10 cases and we excluded studies that reported on upper extremity exostoses or osteochondromas. Demographic and treatment data were collected from each article by two independent authors and collated. A total of 124 abstracts were screened, and 116 articles were reviewed in full, of which 13 met the inclusion criteria.
RESULTS
Complete marginal excision through a fish mouth incision protecting the nail led to a recurrence rate of 4% and satisfactory clinical results, defined as no requirement for postoperative intervention and a satisfactory clinical appearance in 73%. Most studies provided incomplete descriptions of specific surgical techniques used. Fifty-five percent of the patients were younger than 18 years of age. A history of toe trauma before diagnosis was present in approximately 30% of the cases. Delayed diagnosis occurred in approximately 10% of the cases and onychodystrophy occurred in more than 10%.
CONCLUSIONS
There is weak evidence to guide management of subungual exostosis. Adequate wound management postexcision aiming to minimize disruption to the nail bed and matrix may prevent onychodystrophy, which is a common complication of treatment.
Topics: Adolescent; Adult; Age Distribution; Bone Neoplasms; Exostoses; Female; Humans; Hypertrophy; Male; Middle Aged; Nail Diseases; Orthopedic Procedures; Osteochondroma; Patient Satisfaction; Postoperative Complications; Radiography; Recurrence; Sex Distribution; Toe Phalanges; Toes; Treatment Outcome; Young Adult
PubMed: 24146360
DOI: 10.1007/s11999-013-3345-4 -
Orphanet Journal of Rare Diseases Feb 2021Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors,...
BACKGROUND
Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients.
AIM OF STUDY
We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families.
METHODS
Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron-exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis.
RESULTS
EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients.
CONCLUSION
EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME.
Topics: DNA Mutational Analysis; Exons; Exostoses, Multiple Hereditary; Humans; Mutation; N-Acetylglucosaminyltransferases; Saudi Arabia
PubMed: 33632255
DOI: 10.1186/s13023-021-01738-z -
PloS One 2017This paper reports a case of multiple osteochondromas affecting the antlers and the left zygomatic bone of a free-ranging adult white-tailed buck (Odocoileus...
This paper reports a case of multiple osteochondromas affecting the antlers and the left zygomatic bone of a free-ranging adult white-tailed buck (Odocoileus virginianus) from Georgia, USA. Along with a few postcranial bones, the antlered cranium of the individual was found in a severely weathered condition and devoid of any soft tissue. The antlers exhibited five pedunculated exostoses that were composed of cancellous bone and, in their peripheral portions, also mineralized cartilage. The largest of the exostoses, located on the right antler, had a maximum circumference of 55 cm. The exostosis arising from the zygomatic bone was broad-based and much smaller than the exophytic outgrowths on the antlers. Diagnosis of the exostoses as osteochondromas was based on their overall morphology, the normal bone structure in their stalk regions, and the continuity of their spongiosa and cortex with the respective components of the parent bones. Antleromas, i.e., pathological outgrowths developing on antlers as a result of insufficient androgen production, were excluded in the differential diagnosis, based on (1) the apparent maturity and, except for the tumors, normal shape of the antlers and (2) the fact that exostosis formation had also affected the zygomatic bone. Previously only a single case of solitary osteochondroma of an antler has been described in the scientific literature. The case presented here is the first report of multiple osteochondromas in a deer. As antlers are regularly collected as trophies, and huge numbers of them are critically inspected each year, the fact that thus far only two cases of antler osteochondromas have been reported suggests that these tumors are very rare.
Topics: Animals; Antlers; Bone Neoplasms; Deer; Osteochondroma; Skull; Tomography, X-Ray Computed
PubMed: 28296944
DOI: 10.1371/journal.pone.0173775 -
Journal of Medical Genetics Apr 1991
Topics: Adult; Diagnosis, Differential; Exostoses, Multiple Hereditary; Humans; Incidence; Langer-Giedion Syndrome; Male; Radiography; United Kingdom
PubMed: 1856833
DOI: 10.1136/jmg.28.4.262 -
Matrix Biology : Journal of the... Apr 2014Heparan sulfates are complex sulfated molecules found in abundance at cell surfaces and in the extracellular matrix. They bind to and influence the activity of a variety... (Review)
Review
Heparan sulfates are complex sulfated molecules found in abundance at cell surfaces and in the extracellular matrix. They bind to and influence the activity of a variety of molecules like growth factors, proteases and morphogens and are thus involved in various cell-cell and cell-matrix interactions. The mammalian EXT proteins have glycosyltransferase activities relevant for HS chain polymerization, however their exact role in this process is still confusing. In this review, we summarize current knowledge about the biochemical activities and some proposed functions of the members of the EXT protein family and their roles in human disease.
Topics: Amino Acid Sequence; Base Sequence; Exostoses, Multiple Hereditary; Extracellular Matrix; Glycosyltransferases; Heparitin Sulfate; Humans; Models, Molecular; Molecular Sequence Data; Multigene Family; N-Acetylglucosaminyltransferases; Phylogeny; Polymerization; Sequence Alignment; Sequence Analysis, DNA; Species Specificity
PubMed: 24128412
DOI: 10.1016/j.matbio.2013.10.001