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Journal of Children's Orthopaedics Dec 2013Metachondromatosis is a rare genetic disease of osteochondroma and enchondroma formation, caused by loss of function of the PTPN11 gene. It is distinct from other...
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.
PubMed: 24432109
DOI: 10.1007/s11832-013-0526-3 -
BMC Musculoskeletal Disorders Feb 2021This study aimed to investigate the characteristic deformities of the hip in multiple hereditary exostoses patients (MHE) and its association with the hip impingement...
BACKGROUNDS
This study aimed to investigate the characteristic deformities of the hip in multiple hereditary exostoses patients (MHE) and its association with the hip impingement syndrome.
MATERIALS AND METHODS
Between 2001 and 2019, total 51 patients (102 hips) were evaluated in this study. Patients with MHE were classified to femoro-acetabular impingement (FAI) symptom group, ischio-femoral impingement (IFI) symptom group and non-impingement symptom group by comparing the symptoms, clinical signs and imaging studies. To assess the morphometry of the hip in patients with MHE, the femoral neck-shaft angle, Sharp's acetabular angle and center-edge (CE) angle were evaluated. Alpha angle was further evaluated to investigate the FAI using radiographs, and the minimum ischio-femoral distance was further measured to investigate the IFI using computed-tomographic (CT) study.
RESULTS
On hip impingement symptom analysis, FAI symptom and IFI symptom were confirmed in 14 hip joints and 18 hip joints, respectively. Unlike general population, the number of the hip with IFI-symptom was higher than those with FAI symptom in this study. In morphometric evaluation of MHE hips, coxa valga was most prominent deformity with occasional tendency of mild acetabular dysplasia. In a comparison of morphometric study between the impingement symptom group and non-symptom group, the FAI symptom showed significant differences of morphometric measure values than those of the non-symptom group (FAI symptom group vs. Non-FAI symptom group; Femoral neck-shaft angle (153.9 vs 142.6), Sharp's angle (45.0 vs 41.5), CE angle (21.1 vs 28.8) and alpha angle (76.7 vs 57.9)). Similarly, the IFI symptom group also showed significant differences of morphometric measure values than those of the non-symptom group (IFI-symptom vs. Non-IFI symptom; Femoral neck-shaft angle (150.9 vs 142.7), Sharp's angle (44.7 vs 41.4), CE angle (21.1 vs 29.3) and alpha angle (73.3 vs 56.8)). In addition, the minimum ischio-femoral distance measured using CT was significantly decreased in the IFI symptom group (IFI symptom group: 6.6, Non-IFI symptom group: 16.4).
CONCLUSION
The results suggest that the characteristic deformities represented by coxa valga in the MHE hip act as an offset for FAI symptoms, on the contrary, act as a trigger for IFI symptoms.
LEVEL OF EVIDENCE
Level III.
Topics: Exostoses, Multiple Hereditary; Femoracetabular Impingement; Hip Dislocation; Hip Dislocation, Congenital; Hip Joint; Humans
PubMed: 33549073
DOI: 10.1186/s12891-021-04021-1 -
Cureus Jul 2021We describe the case of a 20-year-old man who presented with a bony swelling over the medial proximal tibia that caused pain along the pes anserinus tendons, and a...
We describe the case of a 20-year-old man who presented with a bony swelling over the medial proximal tibia that caused pain along the pes anserinus tendons, and a history of multiple asymptomatic bony swellings. Wide extraperiosteal resection of the swelling relieved the symptoms with a good outcome within a year. This report describes the pictorial pathoanatomy of a relatively rare association of pes anserinus syndrome caused by osteochondroma in an adult patient. Proximal tibial osteochondromas can also present as pes anserinus syndrome in adult patients with diaphyseal aclasis. Large swellings require wide excision to relieve the stretching pain of pes tendons.
PubMed: 34430155
DOI: 10.7759/cureus.16548 -
American Journal of Human Genetics Dec 1954
Topics: Exostoses; Exostoses, Multiple Hereditary; Heredity; Humans
PubMed: 14349947
DOI: No ID Found -
PloS One 2014Hereditary multiple exostoses (HME) is an autosomal dominant disease. The classical paradigm of mutation screening seeks to relate alterations in the exostosin...
BACKGROUND
Hereditary multiple exostoses (HME) is an autosomal dominant disease. The classical paradigm of mutation screening seeks to relate alterations in the exostosin glycosyltransferase genes, EXT1 and EXT2, which are responsible for over 70% of HME cases. However, the pathological significance of the majority of these mutations is often unclear.
METHODS
In a Chinese family with HME, EXT1 and EXT2 genes were screened by direct sequencing. The consequence of a detected mutant was predicted by in silico analysis and confirmed by mRNA analysis. The EXT1 and EXT2 mRNA and protein levels and the HS patterns in the HME patients were compared with those in healthy controls.
RESULTS
A heterozygous transition (c.743+1G>A) in the EXT2 gene, which co-segregated with the HME phenotype in this family, was identified. The G residue at position +1 in intron 4 of EXT2 was predicted to be a 5' donor splice site. The mRNA analysis revealed an alternative transcript with a cryptic splice site 5 bp downstream of the wild-type site, which harbored a premature stop codon. However, the predicted truncated protein was not detected by western blot analysis. Decay of the mutant mRNA was shown by clone sequencing and quantification analysis. The corresponding downregulation of the EXT2 mRNA will contribute to the abnormal EXT1/EXT2 ratio and HS pattern that were detected in the patients with HME.
CONCLUSION
The heterozygous mutation c.743+1G>A in the EXT2 gene causes HME as a result of abnormal splicing, mRNA decay, and the resulting haploinsufficiency of EXT2.
Topics: Alternative Splicing; Bone and Bones; DNA Mutational Analysis; Exostoses, Multiple Hereditary; Female; Genetic Association Studies; Genotype; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Pedigree; RNA Splice Sites; RNA Stability; Radiography
PubMed: 24728384
DOI: 10.1371/journal.pone.0094848 -
The American Journal of Pathology Jun 2015Hereditary multiple exostoses is a pediatric skeletal disorder characterized by benign cartilaginous tumors called exostoses that form next to growing skeletal elements....
Hereditary multiple exostoses is a pediatric skeletal disorder characterized by benign cartilaginous tumors called exostoses that form next to growing skeletal elements. Hereditary multiple exostoses patients carry heterozygous mutations in the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2, but studies suggest that EXT haploinsufficiency and ensuing partial HS deficiency are insufficient for exostosis formation. Searching for additional pathways, we analyzed presence and distribution of heparanase in human exostoses. Heparanase was readily detectable in most chondrocytes, particularly in cell clusters. In control growth plates from unaffected persons, however, heparanase was detectable only in hypertrophic zone. Treatment of mouse embryo limb mesenchymal micromass cultures with exogenous heparanase greatly stimulated chondrogenesis and bone morphogenetic protein signaling as revealed by Smad1/5/8 phosphorylation. It also stimulated cell migration and proliferation. Interfering with HS function both with the chemical antagonist Surfen or treatment with bacterial heparitinase up-regulated endogenous heparanase gene expression, suggesting a counterintuitive feedback mechanism that would result in further HS reduction and increased signaling. Thus, we tested a potent heparanase inhibitor (SST0001), which strongly inhibited chondrogenesis. Our data clearly indicate that heparanase is able to stimulate chondrogenesis, bone morphogenetic protein signaling, cell migration, and cell proliferation in chondrogenic cells. These properties may allow heparanase to play a role in exostosis genesis and pathogenesis, thus making it a conceivable therapeutic target in hereditary multiple exostoses.
Topics: Animals; Cartilage; Cell Line, Tumor; Cell Movement; Cell Proliferation; Child; Chondrocytes; Chondrogenesis; Exostoses, Multiple Hereditary; Glucuronidase; Growth Plate; Humans; Mice; Up-Regulation
PubMed: 25863260
DOI: 10.1016/j.ajpath.2015.02.014 -
Indian Journal of Orthopaedics Sep 2022In this study, we focused on the hip joints and examined pain and functional impairment, and their relationship with anatomical characteristics in MHE patients.
OBJECTIVE
In this study, we focused on the hip joints and examined pain and functional impairment, and their relationship with anatomical characteristics in MHE patients.
METHODS
Patients with MHE followed up in our hospital from January 2020 to December 2020 were enrolled. Clinical hip functional outcomes were evaluated using the Japanese Orthopedic Association (JOA) hip score and hip range of motion (ROM). Proximal femur geometric measurements were evaluated using radiography.
RESULTS
A total of 39 patients (78 hips) with a median age of 25.6 years and average JOA score of 94.0 ± 10.5 were included. Eight patients felt pain in their hip joints. The average ROM score was 18.2 ± 2.5, and 47.4% of the patients with MHE had ROM limitation. The average score of ability to walk was 19.6 ± 1.8, and three patients had some problems with walking. The average ADL score was 18.2 ± 2.5, and 51.3% of patients with MHE had some failures in ADL. The hip flexion and internal rotation were markedly restricted compared with the normal values. When patients were grouped according to their ADL scores, we found that the ADL failure group had a significantly lower ROM score than the no ADL failure group ( < 0.0001), and there were significant differences between the groups in terms of femoral neck widening ( = 0.0001).
CONCLUSIONS
We found that half of MHE patients had some failures in their ADL due to hip functional impairment. The study results also suggest that femoral neck widening affected ADL failure and ROM limitation.
PubMed: 36052379
DOI: 10.1007/s43465-022-00681-w -
Skeletal Radiology Dec 2007In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography,... (Review)
Review
In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI.
Topics: Bone Diseases; Humans; Magnetic Resonance Imaging; Muscular Diseases; Sensitivity and Specificity; Whole Body Imaging
PubMed: 17554538
DOI: 10.1007/s00256-007-0323-5 -
Arthroplasty Today Aug 2022Patients with hereditary multiple exostosis develop several benign osseocartilaginous bulge lesions throughout the body. A 62-year-old woman presented for evaluation of... (Review)
Review
Patients with hereditary multiple exostosis develop several benign osseocartilaginous bulge lesions throughout the body. A 62-year-old woman presented for evaluation of worsening left knee valgus deformity, and left knee pain. She had been diagnosed with hereditary multiple exostosis at the age of 12 years. Radiographic evaluation of the left knee revealed exostoses that caused continuous bulges from cortical bone at the metaphyseal regions of the femur and tibia as well as extra-articular deformity. We used patient-specific instrumentation to indicate the direction of the stem into curved metaphyseal bone regions and then corrected the patient's left knee deformity by performing total knee arthroplasty with titanium-constrained prostheses. Soft tissue release was performed with only complete iliotibial band release at a minimum, and stability was obtained.
PubMed: 35789783
DOI: 10.1016/j.artd.2022.04.017 -
Hand (New York, N.Y.) Jun 2011Hereditary multiple exostosis (HME) is a benign condition with multiple bony tumors with cartilage caps (osteochondromas), mainly presenting in the long and flat bones....
Hereditary multiple exostosis (HME) is a benign condition with multiple bony tumors with cartilage caps (osteochondromas), mainly presenting in the long and flat bones. Usually the presentation for HME is between 2 and 10 years of age and most are seen by 4 years of age (Khan et al. 2009). In this paper, we report a family with three members (father, son, and a daughter) who had very early presentations of HME in the fingers within the first 2 years of age. The son presented with bony nodules at 7 months of age, and he required surgery at 13 months of age for a severe functional deformity of his left ring finger. He also had an unusual histological presentation on his osteochondroma that consists of only subperiosteal cartilage without ossification.
PubMed: 22654707
DOI: 10.1007/s11552-010-9307-3