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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 -
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 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 -
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 -
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 -
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 -
Children (Basel, Switzerland) Jun 2021The hip joint involvement in multiple hereditary exostoses (MHE) occurs in 30-90%, causing pain and limitation of motion by femoroacetabular impingement, coxa valga,...
The hip joint involvement in multiple hereditary exostoses (MHE) occurs in 30-90%, causing pain and limitation of motion by femoroacetabular impingement, coxa valga, acetabular dysplasia, hip joint subluxation, and osteoarthritis. The purpose of this study was to investigate the clinical and radiographic outcomes of ten hips in seven patients treated by surgical dislocation and corrective osteotomies between 2004 and 2009. Surgical dislocation and excision of the osteochondromas and varus intertrochanteric osteotomies were performed in all cases when the neck-shaft angle was > 150°. Common sites of osteochondromas were medial, posterior, and anterior neck of the femur. Neck-shaft angle of the femur was improved from a mean of 157° to 139°, postoperatively. On an average, the center-edge angle improved from 20° to 30° postoperatively. We believe that Ganz's safe surgical dislocation technique is the preferred treatment of MHE. This safeguards the circulation of the femoral head and the osteochondromas can be resected under direct vision. It can be combined with additional corrective osteotomies because the hip affected by MHE is frequently associated with dysplastic changes which can result in premature osteoarthritis.
PubMed: 34201373
DOI: 10.3390/children8060490 -
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 -
Turkish Neurosurgery 2021To investigate the underlying conditions in children with torticollis.
AIM
To investigate the underlying conditions in children with torticollis.
MATERIAL AND METHODS
Between May 2016 and December 2019, 24 patients (10 girls and 14 boys; mean age, 8 years) presenting with twisted neck, neck pain, weakness of extremities, imbalance, and gait disorder were evaluated retrospectively.
RESULTS
Five of the patients had cranial pathologies (cerebellar anaplastic ependymoma and medulloblastoma, brain stem glioma, atypical teratoid rhabdoid tumor, and acute disseminated encephalomyelitis), and five of the patients had spinal pathologies (idiopathic intervertebral disc calcification, vertebral hemangiomatosis, compression fracture, multiple hereditary exostoses, and Langerhans cell histiocytosis at C4). Six of the patients had ocular pathologies (strabismus, Duane syndrome, and Brown syndrome each in two patients). Four patients had otorhinolaryngological infections (Sandifer syndrome, esophageal atresia, reflux, and spasmus nutans, with one patient each). Detailed clinical physical examination and necessary laboratory investigation were performed for all patients.
CONCLUSION
Torticollis is a sign that is not always innocent and may herald an underlying severe disease. Misdiagnosis can lead to wrong and unnecessary surgical procedures and treatments, and sometimes, the results can be damaging due to underlying severe conditions if diagnosed late. In addition, we first report a case of vertebral hemangiomatosis and temporomandibular joint ankylosis that presented with torticollis in the English medical literature.
Topics: Adolescent; Brain Neoplasms; Calcinosis; Child; Child, Preschool; Ependymoma; Eye Diseases; Female; Humans; Infant; Male; Neck Pain; Physical Examination; Retrospective Studies; Spinal Diseases; Torticollis
PubMed: 33759163
DOI: 10.5137/1019-5149.JTN.31359-20.2