-
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 -
Turkish Neurosurgery 2021To investigate the underlying conditions in children with torticollis.
AIM
To investigate the underlying conditions in children with torticollis.
MATERIAL AND METHODS
Between May 2016 and December 2019, 24 patients (10 girls and 14 boys; mean age, 8 years) presenting with twisted neck, neck pain, weakness of extremities, imbalance, and gait disorder were evaluated retrospectively.
RESULTS
Five of the patients had cranial pathologies (cerebellar anaplastic ependymoma and medulloblastoma, brain stem glioma, atypical teratoid rhabdoid tumor, and acute disseminated encephalomyelitis), and five of the patients had spinal pathologies (idiopathic intervertebral disc calcification, vertebral hemangiomatosis, compression fracture, multiple hereditary exostoses, and Langerhans cell histiocytosis at C4). Six of the patients had ocular pathologies (strabismus, Duane syndrome, and Brown syndrome each in two patients). Four patients had otorhinolaryngological infections (Sandifer syndrome, esophageal atresia, reflux, and spasmus nutans, with one patient each). Detailed clinical physical examination and necessary laboratory investigation were performed for all patients.
CONCLUSION
Torticollis is a sign that is not always innocent and may herald an underlying severe disease. Misdiagnosis can lead to wrong and unnecessary surgical procedures and treatments, and sometimes, the results can be damaging due to underlying severe conditions if diagnosed late. In addition, we first report a case of vertebral hemangiomatosis and temporomandibular joint ankylosis that presented with torticollis in the English medical literature.
Topics: Adolescent; Brain Neoplasms; Calcinosis; Child; Child, Preschool; Ependymoma; Eye Diseases; Female; Humans; Infant; Male; Neck Pain; Physical Examination; Retrospective Studies; Spinal Diseases; Torticollis
PubMed: 33759163
DOI: 10.5137/1019-5149.JTN.31359-20.2 -
Orphanet Journal of Rare Diseases Dec 2019Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment... (Review)
Review
BACKGROUND
Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials.
METHODS
A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review.
RESULTS
Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP.
DISCUSSION
It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.
Topics: Animals; Bone Diseases; Female; Humans; Male; Myositis Ossificans; Osteogenesis Imperfecta; Osteopetrosis; Rare Diseases
PubMed: 31888683
DOI: 10.1186/s13023-019-1222-2 -
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 -
Journal of Orthopaedics Dec 2018The purpose of this clinical case-control study was to assess the level of sports activity in children with hereditary multiple exostoses (HME) and to compare with the...
OBJECTIVE
The purpose of this clinical case-control study was to assess the level of sports activity in children with hereditary multiple exostoses (HME) and to compare with the degree of physical activity in children of the same age without pathology.
METHODS
A case-control study was designed. Cases were drawn from children with HME diagnosed on the basis of clinical and radiographic evaluation with an age less then 12 years. Controls were chosen from a group of children with the same age and a negative family history for HME. All patients and controls were completed with the help of parents using the following evaluations: Tegner Activity Level Scale and University of California Los Angeles (UCLA) activity scale.
RESULTS
A total of 154 individuals participated (54 cases and 100 controls). In the case groups, the mean age was 9.07; the mean number of exostoses resulted 29.51, while the mean value of UCLA and Tegner score resulted respectively 6.04 and 5.09. In the controls, the mean age was 8.88; mean UCLA and Tegner resulted respectively 7.17 and 5.64. Comparing the two groups, the only difference was between UCLA score (p = 0.0053). Moreover, comparing the results between female children affected by HME and female controls, we found a significant difference as regards UCLA score (p = 0.0045).
CONCLUSION
Children affected by HME reported lower sports activity, in particular as regards female patients. Moreover, physical activity is not correlated with any other independent factor leading different patients to a similar level of ability in performing sport.
STUDY DESIGN
Level III - Case Control Study.
PubMed: 30190634
DOI: 10.1016/j.jor.2018.08.029 -
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 -
Expert Opinion on Orphan Drugs 2018Hereditary multiple exostoses (HME) is a rare congenital pediatric disorder characterized by osteochondromas forming next to the growth plates in young patients. The...
INTRODUCTION
Hereditary multiple exostoses (HME) is a rare congenital pediatric disorder characterized by osteochondromas forming next to the growth plates in young patients. The osteochondromas cause multiple health problems that include skeletal deformities and chronic pain. Surgery is used to remove the most symptomatic osteochondromas but because of their large number, many are left in place, causing life-long problems and increasing the probability of malignant transformation. There is no other treatment to prevent or reduce osteochondromas formation at present.
AREAS COVERED
Recent studies reviewable through PubMed are providing new insights into cellular and molecular mechanisms of osteochondroma development. The resulting data are suggesting rational and plausible new therapeutic strategies for osteochondroma prevention some of which are being tested in HME animal models and one of which is part of a just announced clinical trial.
EXPERT COMMENTARY
This section summarizes and evaluates such strategies and points also to possible future alternatives.
PubMed: 31448184
DOI: 10.1080/21678707.2018.1483232 -
Cureus Jun 2022The single-bone forearm is a salvage technique for massive loss of bone due to serious trauma, malignant tumors, infections or congenital deformity. It is also...
The single-bone forearm is a salvage technique for massive loss of bone due to serious trauma, malignant tumors, infections or congenital deformity. It is also described to treat the sequelae of hereditary multiple exostoses disease that affects the distal end of the ulna. We present the case of a 29-year-old patient, operated for sequelae of hereditary multiple exostoses disease of the left forearm by a modified single-bone forearm technique. The patient, right-handed, operated on twice in childhood for a hereditary multiple exostoses disease of the left forearm: incomplete excision of the exostosis of the distal end of the ulna and lengthening of this last on external fixator, without improvement. The patient presented for a deformation of the left forearm with shortening compared to the right side. Significant limitation of prono-supination (pronation 15°, supination 20°). Elbow flexion at 110° and extension with deficit of 15°. Wrist flexion at 50° and extension at 50°, radial inclination at 25° and ulnar at 30°. The pain score was 3 according to the Visual Analogue Scale (VAS), especially on effort. Dash score was 31,82/100. We chose the forearm technique with a single bone. The immediate postoperative result found a realignment of the forearm, without neurological or vascular damages. Consolidation was obtained in four months. At five months, the patient recovered elbow flexion at 110° and full extension, wrist flexion at 45° and extension at 50°. Radial inclination at 20° and ulnar at 25°. The single-bone forearm technique has been described, not only for the treatment of hereditary multiple exostoses disease, but also for serious trauma or tumors with massive loss of bone. The technique generally consists of an osteotomy of the radius as well as the ulna, fixing the radius to the ulna creating a synostosis, with or without resection of part of one or both bones of the forearm. The most described complications of single-bone forearm procedure are pain, complications related to soft tissue secondary to the previous injury, and infections. The one-bone forearm remain a salvage technique for massive loss of bone of the forearm, or large deformities due to congenital malformations. This technique could allow the excision of massive bone and keep only a part of the ulna and the radius, with function maintenance and aesthetic forearm preservation.
PubMed: 35903567
DOI: 10.7759/cureus.26361 -
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 -
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