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Best Practice & Research. Clinical... Jun 2020Multiple hereditary exostoses (MHE) and enchondromatosis are rare multifocal benign disorders usually causing skeletal deformities appearing already in childhood. MHE is... (Review)
Review
Multiple hereditary exostoses (MHE) and enchondromatosis are rare multifocal benign disorders usually causing skeletal deformities appearing already in childhood. MHE is a dominant autosomal inherited disorder characterized by multiple osteochondromas (exostoses) growing outward from the metaphyses of long bones as well as from flat bones. They may cause reduced joint motion and pain due to tendon, muscle, and nerve compression. Enchondromatosis (or Ollier's disease) is a noninherited disorder characterized by the presence of multiple intraosseous enchondromas located asymmetrically in the skeleton and with a wide variation regarding location, size, and number ranging from the involvement of a single hand to the involvement of the entire skeleton. It can occur together with soft-tissue hemangiomas in Maffucci's syndrome. Clinical problems caused by the enchondromas are mainly related to skeletal deformities causing malalignment and restricted motion of joint. In both disorders, there is a risk of malignant transformation as well as secondary degenerative joint changes.
Topics: Child; Enchondromatosis; Exostoses, Multiple Hereditary; Humans
PubMed: 32253147
DOI: 10.1016/j.berh.2020.101505 -
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 Journal of Hand Surgery Sep 2021Multiple hereditary exostoses (MHEs) comprise a rare skeletal disorder. This study aimed to elucidate the natural history and characteristics of hand exostoses by...
PURPOSE
Multiple hereditary exostoses (MHEs) comprise a rare skeletal disorder. This study aimed to elucidate the natural history and characteristics of hand exostoses by focusing on their progression or regression and their association with shortening and angular deformation of the finger bones.
METHODS
Of 60 MHE patients who presented to our hospital between 2005 and 2019, 32 patients (62 hands) who underwent hand x-ray examinations were included in a study of initial presentation. Among them, 15 patients (30 hands) who underwent consecutive x-ray examinations before epiphyseal closure were included in a subsequent follow-up study (follow-up period, 6.9 years). We investigated the incidence and common location of hand involvement by exostoses during the initial examination study. We further investigated the progression or regression of hand exostoses and the influence of hand exostoses on longitudinal bone growth and the angular deformation of finger bones during the follow-up study.
RESULTS
In the initial study, we observed exostoses in 30 (60 hands) of 32 (62 hands) patients. The average number of exostoses per hand was 5.2. Exostoses developed more frequently in the middle and ring proximal phalanges and the fifth metacarpal. In the follow-up study, 3.1 exostoses per hand spontaneously regressed and 2.9 exostoses per hand occurred de novo with growth. Progression of exostoses was mainly observed by approximately age 15 years; thereafter, spontaneous regression became dominant. Regression of exostoses was frequently observed in metacarpals, whereas de novo exostoses frequently occurred in phalangeal bones, particularly in distal phalanges. Growth plate involvement by exostoses did not influence the longitudinal growth of finger bones, but it increased their angulation.
CONCLUSIONS
The hand is a common location of exostoses development for MHE patients. Although some exostoses in the hands regress with skeletal maturity, hand involvement by exostoses can result in angular deformity.
TYPE OF STUDY/LEVEL OF EVIDENCE
Diagnostic IV.
Topics: Adolescent; Exostoses, Multiple Hereditary; Follow-Up Studies; Hand; Humans; Metacarpal Bones; Radiography
PubMed: 33642092
DOI: 10.1016/j.jhsa.2020.12.011 -
Skeletal Radiology Apr 2022Ollier disease and Maffucci syndrome are the commonest enchondromatosis subtypes, arising from non-hereditary mutations in the IDH1 and IDH2 genes, presenting in... (Review)
Review
Ollier disease and Maffucci syndrome are the commonest enchondromatosis subtypes, arising from non-hereditary mutations in the IDH1 and IDH2 genes, presenting in childhood and being characterised by multiple enchondromas. Maffucci syndrome also includes multiple soft tissue haemangiomas. Aside from developing bony masses, osseous deformity and pathological fracture, ~ 40% of these patients develop secondary central chondrosarcoma, and there is increased risk of non-skeletal malignancies such as gliomas and mesenchymal ovarian tumours. In this review, we outline the molecular genetics, pathology and multimodality imaging features of solitary enchondroma, Ollier disease and Maffucci syndrome, along with their associated skeletal complications, in particular secondary chondrosarcoma. Given the lifelong risk of malignancy, imaging follow-up will also be explored. Metachondromatosis, a rare enchondromatosis subtype characterised by enchondromas and exostoses, will also be briefly outlined.
Topics: Bone Neoplasms; Chondrosarcoma; Enchondromatosis; Exostoses, Multiple Hereditary; Humans; Syndrome
PubMed: 34302201
DOI: 10.1007/s00256-021-03870-0 -
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 -
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 -
Acta Orthopaedica Belgica Mar 2022There is a high rate of lower limb deformity and limb length discrepancy in patients with hereditary multiple exostoses (HME). The aim of this study was to evaluate the...
There is a high rate of lower limb deformity and limb length discrepancy in patients with hereditary multiple exostoses (HME). The aim of this study was to evaluate the type and frequency of lower limbs axial deviation and limb length discrepancy and the type of exostoses being risk factors for theses deformities. We retrospectively reviewed standing full-length radiograph of 32 HME patients (64 limbs) followed in our institution between October 2009 and December 2020. Patient demographics were recorded. Radiographic analysis of the coronal limb alignment was performed, limb length discrepancy was measured and topography of the exostoses was recorded. We propose a classification of lower legs in 2 groups and 4 types according to the presence and the location of exostoses. In group I, there is an intertibio- fibular exostose with fibular origin at the level of the tibiofibular joints. In type IA, at the level of the distal tibiofibular joint with ascension of the distal fibula; in type IB at the level of the proximal tibiofibular joint with a bracketing effect on the proximal tibia and a lateral slope of the proximal tibial growth plate; the type IC is combining features of both IA and IB. In group II, there is no intertibio-fibular exostose coming from the fibula and no growth abnormality is obvious. A clinically notable lower limb discrepancy (LLD) of ≥2 cm was found in 19% of our patients. Approximately 33% of patients had a knee valgus deformity and 44% had an ankle valgus deformity. The knee valgus deformity was due to fibular growth anomalies and not to distal femur anomalies. The majority of lower legs had fibular growth anomalies (72%) which was a significant risk factor for knee valgus deformity and leg length discrepancy. On the contrary, we found no correlation between number, location and volume of distal femoral exostoses and genu valgum nor leg length discrepancy. Presence of intertibio-fibular exostoses is a risk factor for knee valgus deformity and leg length discrepancy. The presence of these exostoses should lead to a close follow-up of the patient.
Topics: Exostoses, Multiple Hereditary; Fibula; Humans; Leg Length Inequality; Lower Extremity; Retrospective Studies; Tibia
PubMed: 35512172
DOI: 10.52628/88.1.25 -
Journal of Pediatric Orthopedics Mar 2021Multiple hereditary exostoses (MHE) lead to the development of pedunculated or sessile osteocartilaginous lesions. Vertebral involvement occurs in MHE and encroaching...
BACKGROUND
Multiple hereditary exostoses (MHE) lead to the development of pedunculated or sessile osteocartilaginous lesions. Vertebral involvement occurs in MHE and encroaching intracanal exostoses can result in devastating consequences. Magnetic resonance imaging (MRI) of the entire spine has been used to screen for vertebral exostoses to detect high-risk patients. The primary purpose of this investigation is to determine the incidence of vertebral and encroaching intracanal exostoses in patients with MHE. A secondary purpose is to determine if pelvis and rib exostoses serve as "harbinger" lesions of vertebral involvement in MHE.
METHODS
A retrospective chart review was performed on 39 patients (21 male and 18 female individuals) with MHE who underwent routine spinal screening with noncontrast entire spine MRI. The average age at screening was 12.3 years (range, 3 to 17 y). Screening was ordered consecutively on patients seen during the study period who were between ages 8 and 18 years or had complaints that could be related to encroaching intracanal exostoses.
RESULTS
The incidence of vertebral exostoses in this cohort of 39 patients with MHE was 28% (11 total). An encroaching intracanal exostosis was seen in 3 patients (2 cervical, 1 thoracic). Nonencroaching vertebral exostoses were discovered in 8 patients. Sufficient pelvis and rib imaging to determine the presence of pelvis and rib exostoses was available in 8 of those with vertebral exostoses and 19 of those with no vertebral exostoses on screening MRI. In this cohort, the sensitivity and specificity of the presence of both pelvis and rib exostoses for determining the presence of spinal involvement in MHE are 88% and 5%, respectively.
CONCLUSIONS
Based on the results of this cohort, vertebral exostoses are common in MHE, and screening MRI of the entire spine can be used to determine which patients need close observation. If a more selective screening protocol is utilized, an entire spine MRI could be obtained for patients who desire increased physical activity levels or for patients with both pelvis and rib exostoses. At a minimum, treating physicians should monitor patients with MHE closely for neurological symptoms and have a low threshold to obtain advanced spinal imaging.
LEVEL OF EVIDENCE
Level III-diagnostic.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Exostoses, Multiple Hereditary; Female; Humans; Incidence; Magnetic Resonance Imaging; Male; Osteophyte; Retrospective Studies; Spinal Diseases; Spine; Texas
PubMed: 33417389
DOI: 10.1097/BPO.0000000000001749 -
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