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Journal of Children's Orthopaedics Aug 2021The goal of this retrospective study was to compare the gradual lengthening of the ulna in children with multiple hereditary exostoses with and without an elastic...
PURPOSE
The goal of this retrospective study was to compare the gradual lengthening of the ulna in children with multiple hereditary exostoses with and without an elastic intramedullary nail.
METHODS
Between 1998 to 2018, the ulna was lengthened in 28 forearms in 21 patients (aged 7.1 to 16.6 years) using a monolateral external fixator when relative ulnar shortening exceeded 15 mm. In total, 16 forearms were lengthened with the external fixator (group I) and 12 forearms with the addition of an intramedullary elastic nail (group II). Subjective assessment of function, range of movement (ROM) of the wrist and elbow and complications were compared. Ulnar shortening, radial head dislocation, radial articular angle (RAA) and percentage of carpal slip and radial bowing were followed radiographically. The difference between the groups has been evaluated statistically.
RESULTS
The function of the extremity improved partially in 81% of patients in group I and in 83% of patients in group II. ROM was not improved except for radial deviation. Radial head position did not change. The values in group II in comparison with group I are higher for gain of length and lower for bone lengthening index and for bone healing index. Carpal slip decreased insignificantly. The RAA and radial bowing decreased, the comparison of values between groups and age under and over ten years were not statistically significant. Complications were more common in group I. No permanent complications were noted.
CONCLUSION
The addition of an intramedullary nail during the gradual ulnar lengthening improves the gain, bone healing index and rate of complications.
LEVEL OF EVIDENCE
III.
PubMed: 34476028
DOI: 10.1302/1863-2548.15.210002 -
Molecular Genetics and Metabolism... Dec 2021Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of...
BACKGROUND
Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in or ; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions.
METHODS
We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, <50 mmol/d) and high sodium diet (HSD, >200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and I-albumin.
RESULTS
In HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, = 0.058) and increased plasma sodium and effective osmolality.
CONCLUSION
HME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment.
PubMed: 34815940
DOI: 10.1016/j.ymgmr.2021.100797 -
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 -
Medicina (Kaunas, Lithuania) Dec 2022: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations...
: Hereditary multiple exostoses (HME) is a disease characterized by cartilage-capped bony protuberances at the site of growth plates of long bones. Functional mutations in the exostosin genes ( and ) are reported to affect the hedgehog signalling pathways leading to multiple enchondromatosis. However, the exact role of each EXT protein in the regulation of heparan sulphate (HS) chain elongation is still an enigma. In this study, a Pakistani family with HME is investigated to find out the genetic basis of the disease. : Genotyping of eight members of the family by amplifying microsatellite markers, tightly linked to the and genes. : The study revealed linkage of the HME family to the locus 8q24.1. Sanger sequencing identified a heterozygous deletion () in exon 1 of , segregating with the disease phenotype in the family. In silico analysis predicted a shift in the frame causing an early stop codon (p.R83GfsX52). The predicted dwarf protein constituting 134 amino acids was functionally aberrant with a complete loss of the catalytic domain at the C-terminus. Interestingly, an alternative open reading frame 3 (ORF3) caused by the frame shift is predicted to encode a protein sequence, identical to the wild type and containing the catalytic domain, but lacking the first 100 amino acids of the wild-type EXT1 protein. : Consequently, haploinsufficiency could be the cause of HME in the investigated family as the mutated copy of is ineffective for complex formation. The predicted ORF3 protein could be of great significance in understanding several aspects of HME pathogenesis.
Topics: Humans; Exostoses, Multiple Hereditary; Haploinsufficiency; Pakistan; Hedgehog Proteins; Mutation; N-Acetylglucosaminyltransferases; Heparitin Sulfate; Amino Acids
PubMed: 36676722
DOI: 10.3390/medicina59010100 -
Children (Basel, Switzerland) Jun 2021The hip joint involvement in multiple hereditary exostoses (MHE) occurs in 30-90%, causing pain and limitation of motion by femoroacetabular impingement, coxa valga,...
The hip joint involvement in multiple hereditary exostoses (MHE) occurs in 30-90%, causing pain and limitation of motion by femoroacetabular impingement, coxa valga, acetabular dysplasia, hip joint subluxation, and osteoarthritis. The purpose of this study was to investigate the clinical and radiographic outcomes of ten hips in seven patients treated by surgical dislocation and corrective osteotomies between 2004 and 2009. Surgical dislocation and excision of the osteochondromas and varus intertrochanteric osteotomies were performed in all cases when the neck-shaft angle was > 150°. Common sites of osteochondromas were medial, posterior, and anterior neck of the femur. Neck-shaft angle of the femur was improved from a mean of 157° to 139°, postoperatively. On an average, the center-edge angle improved from 20° to 30° postoperatively. We believe that Ganz's safe surgical dislocation technique is the preferred treatment of MHE. This safeguards the circulation of the femoral head and the osteochondromas can be resected under direct vision. It can be combined with additional corrective osteotomies because the hip affected by MHE is frequently associated with dysplastic changes which can result in premature osteoarthritis.
PubMed: 34201373
DOI: 10.3390/children8060490 -
BMC Musculoskeletal Disorders Jan 2021Hereditary multiple exostoses (HME) is a rare skeletal disorder characterised by a widespread. distribution of osteochondromas originating from the metaphyses of long... (Review)
Review
BACKGROUND
Hereditary multiple exostoses (HME) is a rare skeletal disorder characterised by a widespread. distribution of osteochondromas originating from the metaphyses of long bones.
CASE PRESENTATION
This case study examines a 55-year-old male cadaver bequeathed to the University of Liverpool who suffered from HME, thus providing an exceptionally rare opportunity to examine the anatomical changes associated with this condition.
CONCLUSIONS
Findings from imaging and dissection indicated that this was a severe case of HME in terms of the quantity and distribution of the osteochondromas and the number of synostoses present. In addition, the existence of enchondromas and the appearance of gaps within the trabeculae of affected bones make this a remarkable case. This study provides a comprehensive overview of the morbidity of the disease as well as adding to the growing evidence that diseases concerning benign cartilaginous tumours may be part of a spectrum rather than distinct entities.
Topics: Bone Neoplasms; Bone and Bones; Diagnostic Imaging; Exostoses, Multiple Hereditary; Humans; Male; Middle Aged; Osteochondroma
PubMed: 33478453
DOI: 10.1186/s12891-021-03967-6 -
Journal of Chiropractic Medicine Mar 2017The purpose of this report was to describe the presentation of a patient with hereditary multiple exostoses and thoracic spinal cord compression from an osteochondroma.
OBJECTIVE
The purpose of this report was to describe the presentation of a patient with hereditary multiple exostoses and thoracic spinal cord compression from an osteochondroma.
CLINICAL FEATURES
A 31-year-old female presented to a chiropractic clinic with a history of hereditary multiple exostoses and back pain that had existed since the age of 16 years. She had a past medical history that was remarkable for 3 prior surgeries for mass removal. Examination revealed a left upper midscapular mass with decreased sensation.
INTERVENTION/OUTCOME
Magnetic resonance imaging, computed tomography, and biopsy led to a diagnosis of osteochondroma. These diagnostic modalities confirmed that there was no malignant degeneration. Initial magnetic resonance imaging revealed a large expansive lesion involving the left posterior elements at the region of T3-T4. Subsequent thoracic hemilaminectomy and resection of the spinal tumor with posterior instrumentation and stabilization from T2-T5 resulted in 90% overall subjective improvement.
CONCLUSIONS
A detailed case history, thorough examination, guided advanced imaging, and biopsy provide important information for the diagnosis and appropriate treatment of expansive lesions in patients with hereditary multiple exostoses.
PubMed: 28228700
DOI: 10.1016/j.jcm.2016.10.007 -
Connective Tissue Research Jan 2018Multiple hereditary exostoses (MHE) is an autosomal dominant disorder that affects about 1 in 50,000 children worldwide. MHE, also known as hereditary multiple exostoses...
Multiple hereditary exostoses (MHE) is an autosomal dominant disorder that affects about 1 in 50,000 children worldwide. MHE, also known as hereditary multiple exostoses (HME) or multiple osteochondromas (MO), is characterized by cartilage-capped outgrowths called osteochondromas that develop adjacent to the growth plates of skeletal elements in young patients. These benign tumors can affect growth plate function, leading to skeletal growth retardation, or deformations, and can encroach on nerves, tendons, muscles, and other surrounding tissues and cause motion impairment, chronic pain, and early onset osteoarthritis. In about 2-5% of patients, the osteochondromas can become malignant and life threatening. Current treatments consist of surgical removal of the most symptomatic tumors and correction of the major skeletal defects, but physical difficulties and chronic pain usually continue and patients may undergo multiple surgeries throughout life. Thus, there is an urgent need to find new treatments to prevent or reverse osteochondroma formation. The 2016 International MHE Research Conference was convened to provide a forum for the presentation of the most up-to-date and advanced clinical and basic science data and insights in MHE and related fields; to stimulate the forging of new perspectives, collaborations, and venues of research; and to publicize key scientific findings within the biomedical research community and share insights and relevant information with MHE patients and their families. This report provides a description, review, and assessment of all the exciting and promising studies presented at the Conference and delineates a general roadmap for future MHE research targets and goals.
Topics: Animals; Congresses as Topic; Exostoses, Multiple Hereditary; Humans
PubMed: 29099240
DOI: 10.1080/03008207.2017.1394295 -
The Journal of Hand Surgery, European... Mar 2021
Topics: Exostoses, Multiple Hereditary; Forearm; Humans; Reproducibility of Results; Ulna; Wrist Joint
PubMed: 32924768
DOI: 10.1177/1753193420954356 -
Medicina 2023
Topics: Humans; Exostoses, Multiple Hereditary; Spinal Canal
PubMed: 37379552
DOI: No ID Found