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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 -
Diagnostic and Interventional Imaging Jan 2017Exostoses are the most common benign bone tumors, accounting for 10 to 15% of all bone tumors. They develop at the bone surface by enchondral ossification and stop... (Review)
Review
Exostoses are the most common benign bone tumors, accounting for 10 to 15% of all bone tumors. They develop at the bone surface by enchondral ossification and stop growing when skeletal maturity has been reached. At first, exostoses are covered by a smooth cartilage cap that progressively ossifies with skeleton maturity. Then they may regress, partly or even completely. Osteochondromas may be solitary or multiple, with the latter associated with hereditary multiple exostoses (HME). Exostoses develop during childhood and become symptomatic during the third decade of life in the case of solitary exostoses, or earlier, in case of HME. They stop growing after puberty, when the epiphyseal plates close. Most exostoses remain asymptomatic. Local complications, usually benign, may occur, such as fractures or mechanical impingements upon nearby structures. In rare cases, sarcomatous degeneration occurs. Most of these complications have been described in case reports. This article describes the imaging features of benign complications of exostoses of the shoulder, pelvic girdles and appendicular.
Topics: Aneurysm, False; Bone Neoplasms; Bone and Bones; Bursa, Synovial; Exostoses; Fractures, Bone; Humans; Nerve Compression Syndromes; Osteochondroma; Shoulder Impingement Syndrome; Vascular Diseases
PubMed: 27316575
DOI: 10.1016/j.diii.2015.11.021 -
Journal of Pediatric Neurosciences 2021Osteoid osteoma is a benign bony pathology. It presents either as a solitary lesion or as multiple lesions with a genetic predisposition. Reported more often in...
Osteoid osteoma is a benign bony pathology. It presents either as a solitary lesion or as multiple lesions with a genetic predisposition. Reported more often in teenagers with thrice more common incidence among boys than in girls, it has a predilection for long bones of lower limbs. Less commonly arising from iliac crest or ribs; it is seen to be further rare to have originated from vertebrae or tarsal/carpal bones. Cranial osteomas are detected either incidentally on imaging or present as a bony hard swelling arising from the skull. Spinal intracanal osteomas are extremely rare to encounter in clinical practice. C in a case of ) presenting with myelopathy is further rare. Less than thirty such cases have been reported so far. We present here a rare case of HME in a 16-year-old boy with compressive myelopathy secondary to intracanal cervical osteoma at C4 Lamina and spinous process. He had a phenotypical expression of hereditary multiple osteomas with a strong family history of inheritance of trait among first-degree male relatives favoring genetic transmission of disease with variable penetrance. All reported cases, to date, are discussed in a tabulated form.
PubMed: 36160610
DOI: 10.4103/jpn.JPN_39_20 -
Cureus Jun 2022The single-bone forearm is a salvage technique for massive loss of bone due to serious trauma, malignant tumors, infections or congenital deformity. It is also...
The single-bone forearm is a salvage technique for massive loss of bone due to serious trauma, malignant tumors, infections or congenital deformity. It is also described to treat the sequelae of hereditary multiple exostoses disease that affects the distal end of the ulna. We present the case of a 29-year-old patient, operated for sequelae of hereditary multiple exostoses disease of the left forearm by a modified single-bone forearm technique. The patient, right-handed, operated on twice in childhood for a hereditary multiple exostoses disease of the left forearm: incomplete excision of the exostosis of the distal end of the ulna and lengthening of this last on external fixator, without improvement. The patient presented for a deformation of the left forearm with shortening compared to the right side. Significant limitation of prono-supination (pronation 15°, supination 20°). Elbow flexion at 110° and extension with deficit of 15°. Wrist flexion at 50° and extension at 50°, radial inclination at 25° and ulnar at 30°. The pain score was 3 according to the Visual Analogue Scale (VAS), especially on effort. Dash score was 31,82/100. We chose the forearm technique with a single bone. The immediate postoperative result found a realignment of the forearm, without neurological or vascular damages. Consolidation was obtained in four months. At five months, the patient recovered elbow flexion at 110° and full extension, wrist flexion at 45° and extension at 50°. Radial inclination at 20° and ulnar at 25°. The single-bone forearm technique has been described, not only for the treatment of hereditary multiple exostoses disease, but also for serious trauma or tumors with massive loss of bone. The technique generally consists of an osteotomy of the radius as well as the ulna, fixing the radius to the ulna creating a synostosis, with or without resection of part of one or both bones of the forearm. The most described complications of single-bone forearm procedure are pain, complications related to soft tissue secondary to the previous injury, and infections. The one-bone forearm remain a salvage technique for massive loss of bone of the forearm, or large deformities due to congenital malformations. This technique could allow the excision of massive bone and keep only a part of the ulna and the radius, with function maintenance and aesthetic forearm preservation.
PubMed: 35903567
DOI: 10.7759/cureus.26361 -
Journal of Clinical Medicine Jun 2022Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical...
Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of MHE using our own scoring system and analyzed the risk factors associated with severe clinical phenotypes. In this study, 43 patients from 30 families were analyzed. The mutations were identified by direct sequencing of polymerase chain reaction-amplified genomic DNA or by multiplex ligation-dependent probe amplification. According to a new scoring system devised by the authors, the severity of the phenotype was assessed as mild, moderate, or severe based on the deformity of each segment, number of exostoses, leg length discrepancy, and functional limitations. Of 43 patients from 30 families, 39 patients (90.7%) and 24 families (80%) presented with EXT1 or EXT2 mutations. Patients with EXT1 mutations had a significantly worse phenotype than that of patients with EXT2 mutations or without any detectable mutation. The mean clinical score of patients with an EXT1 mutation (5.76; range, 2.0-8.0; SD = 1.60) was higher than that of patients with an EXT2 mutation (4.06; range, 2.0-7.0; SD = 1.47) or of those without any detectable mutation (4.63; range, 3.0-6.0; SD = 1.44; = 0.005). According to our classification system, more patients with EXT1 mutations had 'severe disease' than those with EXT2 mutations. Deformity scores were also higher in patients with EXT1 mutations ( = 0.018). In the multivariate analysis, the deformity score was found to be associated with the 'severe' class ( = 0.031). In conclusion, 90.7% of patients with MHE showed EXT mutations. Our scoring system showed reliable results. We suggest that the extent of deformity is an important factor in determining the phenotype of MHE and close monitoring for the development of severe disease is recommended in patients with high deformity scores.
PubMed: 35806987
DOI: 10.3390/jcm11133703 -
Expert Opinion on Orphan Drugs 2018Hereditary multiple exostoses (HME) is a rare congenital pediatric disorder characterized by osteochondromas forming next to the growth plates in young patients. The...
INTRODUCTION
Hereditary multiple exostoses (HME) is a rare congenital pediatric disorder characterized by osteochondromas forming next to the growth plates in young patients. The osteochondromas cause multiple health problems that include skeletal deformities and chronic pain. Surgery is used to remove the most symptomatic osteochondromas but because of their large number, many are left in place, causing life-long problems and increasing the probability of malignant transformation. There is no other treatment to prevent or reduce osteochondromas formation at present.
AREAS COVERED
Recent studies reviewable through PubMed are providing new insights into cellular and molecular mechanisms of osteochondroma development. The resulting data are suggesting rational and plausible new therapeutic strategies for osteochondroma prevention some of which are being tested in HME animal models and one of which is part of a just announced clinical trial.
EXPERT COMMENTARY
This section summarizes and evaluates such strategies and points also to possible future alternatives.
PubMed: 31448184
DOI: 10.1080/21678707.2018.1483232 -
Journal of Orthopaedics Dec 2018The purpose of this clinical case-control study was to assess the level of sports activity in children with hereditary multiple exostoses (HME) and to compare with the...
OBJECTIVE
The purpose of this clinical case-control study was to assess the level of sports activity in children with hereditary multiple exostoses (HME) and to compare with the degree of physical activity in children of the same age without pathology.
METHODS
A case-control study was designed. Cases were drawn from children with HME diagnosed on the basis of clinical and radiographic evaluation with an age less then 12 years. Controls were chosen from a group of children with the same age and a negative family history for HME. All patients and controls were completed with the help of parents using the following evaluations: Tegner Activity Level Scale and University of California Los Angeles (UCLA) activity scale.
RESULTS
A total of 154 individuals participated (54 cases and 100 controls). In the case groups, the mean age was 9.07; the mean number of exostoses resulted 29.51, while the mean value of UCLA and Tegner score resulted respectively 6.04 and 5.09. In the controls, the mean age was 8.88; mean UCLA and Tegner resulted respectively 7.17 and 5.64. Comparing the two groups, the only difference was between UCLA score (p = 0.0053). Moreover, comparing the results between female children affected by HME and female controls, we found a significant difference as regards UCLA score (p = 0.0045).
CONCLUSION
Children affected by HME reported lower sports activity, in particular as regards female patients. Moreover, physical activity is not correlated with any other independent factor leading different patients to a similar level of ability in performing sport.
STUDY DESIGN
Level III - Case Control Study.
PubMed: 30190634
DOI: 10.1016/j.jor.2018.08.029 -
Hand (New York, N.Y.) Dec 2015The purpose is to determine the location and type of osteochondromas in patients with multiple osteochondroma of the hand as well as the presence of shortening and... (Review)
Review
BACKGROUND
The purpose is to determine the location and type of osteochondromas in patients with multiple osteochondroma of the hand as well as the presence of shortening and angulation. Second, it aims to establish longitudinal data on the change in tumors.
METHODS
Retrospective review of patients with multiple osteochondroma affecting the hand evaluating the location and type of tumors as well as the presence of shortening and angulation is done. We examined radiographs from final follow-up and analyzed them based on patient age at presentation (group I = ages 2-6; II = ages 7-10; III = ages 11-19), to determine changes over time and any differences in the number of tumors, location, and shortening and angulation.
RESULTS
The most affected bones were the index and small finger metacarpals with an increase seen around the metacarpophalangeal (MCP) joints. The most shortening and angulation were seen on the ulnar side. Group II had the most tumors and the most bones with angulation. Twenty-three hands had longitudinal follow-up with an overall increase of 2.7 tumors per hand with a range of loss of 8 to gain of 16. There was an increase in the number of bones with angulation and shortening. Group I showed the largest increase in tumors, shortening, and angulation.
CONCLUSIONS
The ulnar side and bones around the MCP joints are affected most commonly. The largest change was seen as the patients went from young childhood into adolescence, which may be due to rapid growth during this time. This is the largest study of these patients with the longest longitudinal data.
PubMed: 26568714
DOI: 10.1007/s11552-015-9775-6 -
BMJ Case Reports Aug 2019Osteochondroma is the most common type of benign bone tumour. It is a benign chondrogenic lesion derived from aberrant cartilage from the perichondral ring, and it...
Osteochondroma is the most common type of benign bone tumour. It is a benign chondrogenic lesion derived from aberrant cartilage from the perichondral ring, and it commonly presents in the proximal humerus, proximal femur and knee. Osteochondroma is usually solitary but can be multiple with patients with hereditary multiple exostoses. Malignant changes happen in approximately 1% of cases. Osteochondroma usually causes local pain or swelling. We discuss a unique case of an osteochondroma that highlights the fact that osteochondroma can occur in the most unlikely places, and they should be properly visualised via radiography to evaluate any extensions and compromised surrounding structures before surgical intervention.
Topics: Acromioclavicular Joint; Bone Neoplasms; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteochondroma; Range of Motion, Articular; Tomography, X-Ray Computed
PubMed: 31444263
DOI: 10.1136/bcr-2019-230246 -
Bone Apr 2018The majority of skeletal elements develop via endochondral ossification. This process starts with formation of mesenchymal cell condensations at prescribed sites and... (Review)
Review
The majority of skeletal elements develop via endochondral ossification. This process starts with formation of mesenchymal cell condensations at prescribed sites and times in the early embryo and is followed by chondrogenesis, growth plate cartilage maturation and hypertrophy, and replacement of cartilage with bone and marrow. This complex stepwise process is reactivated and recapitulated in physiologic conditions such as fracture repair, but can occur extraskeletally in pathologies including heterotopic ossification (HO), Ossification of the Posterior Longitudinal Ligament (OPLL) and Hereditary Multiple Exostoses (HME). One form of HO is common and is triggered by trauma, invasive surgeries or burns and is thus particularly common amongst severely wounded soldiers. There is also a congenital and very severe form of HO that occurs in children with Fibrodysplasia Ossificans Progressiva (FOP) and is driven by activating mutations in ACVR1 encoding the type I bone morphogenetic protein (BMP) receptor ALK2. Current treatments for acquired HO, including NSAIDs and local irradiation, are not always effective and can have side effects, and there is no effective treatment for HO in FOP. This review article describes the research path we took several years ago to develop a new and effective treatment for both congenital and acquired forms of HO and specifically, the testing of synthetic retinoid agonists to block the initial and critical chondrogenic step leading to HO onset and progression. We summarize studies with mouse models of injury-induced and congenital HO demonstrating the effectiveness and mode of action of the retinoid agonists, including Palovarotene. Our studies have provided the rationale for, directly led to, an ongoing phase 2 FDA clinical trial to test efficacy and safety of Palovarotene in FOP. Top-line results released a few months ago by the pharmaceutical sponsor Clementia are very encouraging. Given shared developmental pathways amongst pathologies of extraskeletal tissue formation, Palovarotene may also be effective in HME as preliminary in vitro data suggest.
Topics: Animals; Chondrogenesis; Humans; Myositis Ossificans; Ossification, Heterotopic; Osteogenesis; Retinoids; Signal Transduction
PubMed: 28826842
DOI: 10.1016/j.bone.2017.08.010