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Indian Pediatrics Feb 2021
Topics: Bone Neoplasms; Exostoses; Humans; Nail Diseases; Osteochondroma; Toes
PubMed: 33632969
DOI: No ID Found -
The Pan African Medical Journal 2022
Topics: Bone Neoplasms; Humans; Osteochondroma; Ribs
PubMed: 35949455
DOI: 10.11604/pamj.2022.42.59.35217 -
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 -
The American Journal of Pathology Dec 2021Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal... (Review)
Review
Osteochondromas are cartilage-capped tumors that arise near growing physes and are the most common benign bone tumor in children. Osteochondromas can lead to skeletal deformity, pain, loss of motion, and neurovascular compression. Currently, surgery is the only available treatment for symptomatic osteochondromas. Osteochondroma mouse models have been developed to understand the pathology and the origin of osteochondromas and develop therapeutic drugs. Several cartilage regulatory pathways have been implicated in the development of osteochondromas, such as bone morphogenetic protein, hedgehog, and WNT/β-catenin signaling. Retinoic acid receptor-γ is an important regulator of endochondral bone formation. Selective agonists for retinoic acid receptor-γ, such as palovarotene, have been investigated as drugs for inhibition of ectopic endochondral ossification, including osteochondromas. This review discusses the signaling pathways involved in osteochondroma pathogenesis and their possible interactions with the retinoid pathway.
Topics: Animals; Bone Neoplasms; Disease Models, Animal; Humans; Mice; Osteochondroma; Retinoids; Signal Transduction
PubMed: 34809786
DOI: 10.1016/j.ajpath.2021.08.003 -
Indian Journal of Dermatology,... 2017
Topics: Bone Neoplasms; Child; Exostoses; Female; Humans; Nail Diseases; Osteochondroma
PubMed: 28474643
DOI: 10.4103/ijdvl.IJDVL_931_16 -
Archives of Pathology & Laboratory... Jan 2022A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically... (Review)
Review
CONTEXT.—
A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically been thought to be reactive lesions. However, modern molecular techniques when supplementing clinical, radiographic, and histologic evaluation suggest they may, in fact, be neoplasms.
OBJECTIVE.—
To review the clinical presentation and histopathologic, molecular, and radiologic features of selective bone lesions, focusing most specifically on subungual exostosis, florid reactive periostitis, and bizarre periosteal osteochondromatous proliferation.
DATA SOURCES.—
Literature review and personal experience are the sources of this review.
CONCLUSIONS.—
Some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities, and thus may be neoplasms. Although most common in the bones of the fingers and toes, these lesions also occur in long and other bones. The clinical presentations, radiologic appearances, and histopathologic features often overlap, making the diagnosis challenging, and these lesions may require molecular evaluation to maximize accurate prognostication.
Topics: Bone Neoplasms; Diagnosis, Differential; Exostoses; Hand; Humans; Osteochondroma; Periostitis
PubMed: 33946096
DOI: 10.5858/arpa.2020-0817-RA -
Matrix Biology : Journal of the... Oct 2018Heparan sulfate (HS) is an essential component of cell surface and matrix proteoglycans (HS-PGs) that include syndecans and perlecan. Because of their unique structural... (Review)
Review
Heparan sulfate (HS) is an essential component of cell surface and matrix proteoglycans (HS-PGs) that include syndecans and perlecan. Because of their unique structural features, the HS chains are able to specifically interact with signaling proteins -including bone morphogenetic proteins (BMPs)- via their HS-binding domain, regulating protein availability, distribution and action on target cells. Hereditary Multiple Exostoses (HME) is a rare pediatric disorder linked to germline heterozygous loss-of-function mutations in EXT1 or EXT2 that encode Golgi-resident glycosyltransferases responsible for HS synthesis, resulting in a systemic HS deficiency. HME is characterized by cartilaginous/bony tumors -called osteochondromas or exostoses- that form within perichondrium in long bones, ribs and other elements. This review examines most recent studies in HME, framing them in the context of classic studies. New findings show that the spectrum of EXT mutations is larger than previously realized and the clinical complications of HME extend beyond the skeleton. Osteochondroma development requires a somatic "second hit" that would complement the germline EXT mutation to further decrease HS production and/levels at perichondrial sites of osteochondroma induction. Cellular studies have shown that the steep decreases in local HS levels: derange the normal homeostatic signaling pathways keeping perichondrium mesenchymal; cause excessive BMP signaling; and provoke ectopic chondrogenesis and osteochondroma formation. Data from HME mouse models have revealed that systemic treatment with a BMP signaling antagonist markedly reduces osteochondroma formation. In sum, recent studies have provided major new insights into the molecular and cellular pathogenesis of HME and the roles played by HS deficiency. These new insights have led to the first ever proof-of-principle demonstration that osteochondroma formation is a druggable process, paving the way toward the creation of a clinically-relevant treatment.
Topics: Animals; Bone Morphogenetic Proteins; Disease Models, Animal; Exostoses, Multiple Hereditary; Heparitin Sulfate; Humans; Mice; Mutation; N-Acetylglucosaminyltransferases; Signal Transduction
PubMed: 29277722
DOI: 10.1016/j.matbio.2017.12.011 -
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