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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 -
Proceedings of the Royal Society of... Jul 1947
Topics: Enchondromatosis; Exostoses, Multiple Hereditary; Osteochondrodysplasias
PubMed: 19993593
DOI: No ID Found -
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 -
Acta Reumatologica Portuguesa 2012
Topics: Child, Preschool; Exostoses, Multiple Hereditary; Humans; Male
PubMed: 22781520
DOI: No ID Found -
Journal of Comparative Pathology Aug 2023Feline osteochondromatosis is a spontaneous osteocartilaginous exostosis associated with feline leukaemia virus (FeLV) infection or due to a frameshift variant in the...
Feline osteochondromatosis is a spontaneous osteocartilaginous exostosis associated with feline leukaemia virus (FeLV) infection or due to a frameshift variant in the exostosin glycosyltransferase 1 (EXT1) gene. Osteochondromatosis was diagnosed in an indoor-only, 12-year-old, neutered female, Russian Blue cat. Radiographs revealed bilateral calcified proliferations in the elbow, costochondral and sternochondral joints, which distorted the normal skeletal structure. Grossly, the proliferated joints presented with consistent, rounded masses, causing complete ankylosis. The main histopathological finding was an osteocartilaginous proliferation composed of multiple irregular islands of well-differentiated hyaline cartilage surrounded and delimited by osteoid tissue. Immunohistochemistry of the osteochondromas, bone marrow and mediastinal lymph nodes, using a primary anti-FeLV gp70 antibody, and FeLV proviral DNA real-time polymerase chain reaction on bone marrow were negative. Sequencing of exon 6 of the EXT1 gene was performed and nucleotide BLAST analysis demonstrated the absence of a frameshift variant. This study reports the only case of spontaneous feline osteochondromatosis in an animal more than 10 years old.
Topics: Female; Cats; Animals; Leukemia Virus, Feline; Osteochondromatosis; Leukemia, Feline; Exons; Ankylosis; Cat Diseases
PubMed: 37597496
DOI: 10.1016/j.jcpa.2023.07.003 -
Genes Nov 2022Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal...
Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, and In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% ( = 14) had a family history of MO. Clinical severity scores were class I in 34% (:18), class II in 24.5% (:13) and class III in 41.5% (:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in and 11 (38%) in . Patients with variants showed a height z-score of 1.03 SD lower than those with variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.
Topics: Humans; Exostoses, Multiple Hereditary; Cross-Sectional Studies; N-Acetylglucosaminyltransferases; Mutation; Genetic Testing
PubMed: 36360300
DOI: 10.3390/genes13112063 -
Journal of Pediatric Orthopedics 2011Multiple hereditary exostoses, also termed as multiple osteochondromas, is a heritable disorder of connective tissue with primarily orthopaedic clinical manifestations.... (Review)
Review
BACKGROUND
Multiple hereditary exostoses, also termed as multiple osteochondromas, is a heritable disorder of connective tissue with primarily orthopaedic clinical manifestations. Understanding of its biological underpinnings has been advanced on a variety of fronts in recent years.
METHODS
The multifaceted literature regarding osteochondromagenesis and the major clinical challenges in patients with multiple osteochondromas were reviewed.
RESULTS
Consideration of recent advances in molecular biology, biochemistry, and animal modeling of osteochondroma pathogenesis yields a unified model.
CONCLUSIONS
Mechanistic details and therapeutic targets have yet to be elucidated, but the general biology of osteochondroma formation is increasingly clear, as well as its implications in the orthopaedic clinical setting.
Topics: Animals; Exostoses, Multiple Hereditary; Glycomics; Growth Plate; Humans
PubMed: 21654469
DOI: 10.1097/BPO.0b013e31821c7738 -
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 -
Medicina 2023
Topics: Humans; Exostoses, Multiple Hereditary; Spinal Canal
PubMed: 37379552
DOI: No ID Found -
Italian Journal of Pediatrics Jun 2020Hereditary multiple osteochondromas (HMO) is a genetic condition characterized by the presence of multiple osteochondromas, usually at the lateral side of the most...
BACKGROUND
Hereditary multiple osteochondromas (HMO) is a genetic condition characterized by the presence of multiple osteochondromas, usually at the lateral side of the most active growth plate of a long bone. These lesions may persist, be asymptomatic during childhood, and may increase in number and size until growth plates close. Therefore, diagnosis of HMO in children and young people can be challenging; while short stature can be more evident at the onset of puberty, asymptomatic ostheocondromas can progress into different degrees of orthopedic deformity. Moreover, multiple complications may arise due to the presence of osteochondromas, including tendon and compression muscle pain, neurovascular disorders, obstetric problems, scoliosis and malignant transformation into secondary peripheral chondrosarcoma in adulthood.
CASE PRESENTATION
We report the case of a girl admitted to our Institute for growth delay. While laboratory tests, including growth hormone stimulation test, were normal, left hand X-ray revealed multiple osteochondromas, suggestive for HMO. The genetic test for EXT1 and EXT2 genes confirmed the radiological diagnosis, with a mutation inherited from the mother who displayed the same radiological abnormalities along with recurrent limb pain episodes.
CONCLUSIONS
HMO is a genetic condition whose diagnosis can be challenging, especially in females. Every pediatricians should consider a skeletal dysplasia in case of unexplained growth delay and a skeletal survey might be fundamental in reaching a diagnosis.
Topics: Adolescent; Exostoses, Multiple Hereditary; Female; Genetic Testing; Humans; Radiography
PubMed: 32522262
DOI: 10.1186/s13052-020-00846-z