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Annals of Cardiac Anaesthesia 2018We report a rare case of multiple hereditary exostosis where patient presented with bilateral base of neck exostoses with concurrent compression of brachial plexus and...
We report a rare case of multiple hereditary exostosis where patient presented with bilateral base of neck exostoses with concurrent compression of brachial plexus and subclavian artery and vein. The patient was a young 26-year-old woman with chief complaints of pain in the left upper extremity, paresthesia in the left ring and little finger, and weakness in hand movement and grip. On referral, history, physical examination, radiological imaging, and electrodiagnostic tests evaluated the patient. Due to severe pain and disability in performing routine activities, surgical intervention was necessary. In the current case, the patient had thoracic outlet syndrome with concomitant venous, arterial, and neurogenic sub types. Radial pulse returned and pain associated with brachial plexus compression was resolved after the surgery.
Topics: Adult; Exostoses, Multiple Hereditary; Female; Humans; Thoracic Outlet Syndrome
PubMed: 29336398
DOI: 10.4103/aca.ACA_119_17 -
HSS Journal : the Musculoskeletal... Sep 2005
PubMed: 18751809
DOI: 10.1007/s11420-005-0107-1 -
American Journal of Human Genetics Sep 1997Hereditary multiple exostoses (HME), the most frequent of all skeletal dysplasias, is an autosomal dominant disorder characterized by the presence of multiple exostoses...
Hereditary multiple exostoses (HME), the most frequent of all skeletal dysplasias, is an autosomal dominant disorder characterized by the presence of multiple exostoses localized mainly at the end of long bones. HME is genetically heterogeneous, with at least three loci, on 8q24.1 (EXT1), 11p11-p13 (EXT2), and 19p (EXT3). Both the EXT1 and EXT2 genes have been cloned recently and define a new family of potential tumor suppressor genes. This is the first study in which mutation screening has been performed for both the EXT1 and EXT2 genes prior to any linkage analysis. We have screened 17 probands with the HME phenotype, for alterations in all translated exons and flanking intronic sequences, in the EXT1 and EXT2 genes, by conformation-sensitive gel electrophoresis. We found the disease-causing mutation in 12 families (70%), 7 (41%) of which have EXT1 mutations and 5 (29%) EXT2 mutations. Together with the previously described 1-bp deletion in exon 6, which is present in 2 of our families, we report five new mutations in EXT1. Two are missense mutations in exon 2 (G339D and R340C), and the other three alterations (a nonsense mutation, a frameshift, and a splicing mutation) are likely to result in truncated nonfunctional proteins. Four new mutations are described in EXT2. A missense mutation (D227N) was found in 2 different families; the other three alterations (two nonsense mutations and one frameshift mutation) lead directly or indirectly to premature stop codons. The missense mutations in EXT1 and EXT2 may pinpoint crucial domains in both proteins and therefore give clues for the understanding of the pathophysiology of this skeletal disorder.
Topics: Electrophoresis, Polyacrylamide Gel; England; Exostoses, Multiple Hereditary; Female; Genes, Tumor Suppressor; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Pedigree; Polymerase Chain Reaction; Proteins
PubMed: 9326317
DOI: 10.1086/515505 -
Journal of Vascular and Interventional... Feb 2015Vascular complications related to multiple hereditary exostoses are uncommon. We present a 39-year-old male patient with multiple exostoses in the upper and lower limbs...
UNLABELLED
Vascular complications related to multiple hereditary exostoses are uncommon. We present a 39-year-old male patient with multiple exostoses in the upper and lower limbs with an associated positive familial history of such lesions. He experienced a sudden onset of left-side ataxia and hypoesthesia secondary to a left lateral medullary infarction, which was due to a stenotic-pattern vertebral artery dissection (V1-V4). This complication is very rare as a differential diagnosis in the vertebro-basilar dissection spectrum, and a nonspecific relation has been found.
ABBREVIATIONS
MHEMultiple hereditary exostosesATangiotomographyVADvertebral artery dissectionCADcervical artery dissectionOIosteogenesis imperfecta.
PubMed: 25825632
DOI: No ID Found -
BMJ Case Reports Sep 2021Ischiofemoral impingement (IFI) has been described in the medical literature as a cause of hip pain. IFI occurs due to an abnormal contact or reduced space between the...
Ischiofemoral impingement (IFI) has been described in the medical literature as a cause of hip pain. IFI occurs due to an abnormal contact or reduced space between the lesser trochanter and the lateral border of the ischium and is an often unrecognised cause of pain and snapping in the hip. Association of multiple exostoses and a skeletal dysplasia characterised by an abnormal modelling of bone metaphysis and osseous deformities is highly characteristic of this disease. Consequently, multiple exostoses may narrow the ischiofemoral space and cause impingement and pain, even in the absence of malignant transformation. Surgical excision of exostosis of the lesser trochanter is a safe and effective method of treatment for patients with IFI. We present a case of left hip pain with incidental finding of hereditary multiple osteochondroma causing IFI and discuss the predisposing factors and review of literature.
Topics: Adult; Bone Neoplasms; Exostoses, Multiple Hereditary; Femoracetabular Impingement; Hip Joint; Humans; Incidental Findings; Ischium
PubMed: 34518173
DOI: 10.1136/bcr-2021-241840 -
Heliyon Jan 2023Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether...
BACKGROUND
Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether NFAT signaling is also involved in human osteochondromagenesis. As the first step in addressing this question, the current study aimed to determine the expression patterns of NFATC1 and NFATC2 in human osteochondroma samples.
METHODS
Immunohistochemistry (IHC) was used to examine and analyze NFATC1 and NFATC2 expression in human osteochondroma samples. The human periosteum was used to map the expression of NFATC1 under physiological conditions by IHC. Furthermore, human periosteal progenitors were isolated and identified from the periosteal tissues of bone fracture healing patients. The expression of NFATC1 in human periosteal progenitors was characterized by Western blotting compared to human bone marrow stromal cells (BMSC).
RESULTS
The IHC results showed that the expression of NFATC1 was undetectable in most human osteochondromas cells, and only a small proportion of osteochondroma cells, especially clonally grown chondrocytes, showed positive staining of NFATC1. NFATC2 expression was also undetectable in most chondrocytes in human osteochondromas. The mouse and human periosteum showed a comparable ratio of NFATC1 positive cells (9.56 ± 0.80% 11.04 ± 2.05%, = 0.3101). Furthermore, Western blotting analysis revealed that NFATC1 expression was highly enriched in human periosteal progenitors compared to BMSC.
CONCLUSIONS
NFATC1 and NFATC2 are undetectable in most human osteochondroma chondrocytes. The expression pattern of NFATC1 in human osteochondromas and the normal periosteum suggests that NFAT signaling could be suppressed during human osteochondromagenesis.
PubMed: 36747924
DOI: 10.1016/j.heliyon.2023.e13018 -
Bone May 2011Multiple Hereditary Exostoses (MHE) syndrome is caused by haploinsufficiency in Golgi-associated heparan sulfate polymerases EXT1 or EXT2 and is characterized by...
Multiple Hereditary Exostoses (MHE) syndrome is caused by haploinsufficiency in Golgi-associated heparan sulfate polymerases EXT1 or EXT2 and is characterized by formation of exostoses next to growing long bones and other skeletal elements. Recent mouse studies have indicated that formation of stereotypic exostoses requires a complete loss of Ext expression, suggesting that a similar local loss of EXT function may underlie exostosis formation in patients. To further test this possibility and gain greater insights into pathogenic mechanisms, we created heterozygous Ext1(+/-) and compound Ext1(+/-)/Ext2(+/-) mice. Like Ext2(+/-) mice described previously (Stickens et al. Development 132:5055), Ext1(+/-) mice displayed rib-associated exostosis-like outgrowths only. However, compound heterozygous mice had nearly twice as many outgrowths and, more importantly, displayed stereotypic growth plate-like exostoses along their long bones. Ext1(+/-)Ext2(+/-) exostoses contained very low levels of immuno-detectable heparan sulfate, and Ext1(+/-)Ext2(+/-) chondrocytes, endothelial cells and fibroblasts in vitro produced shortened heparan sulfate chains compared to controls and responded less vigorously to exogenous factors such as FGF-18. We also found that rib outgrowths formed in Ext1(f/+)Col2Cre and Ext1(f/+)Dermo1Cre mice, suggesting that ectopic skeletal tissue can be induced by conditional Ext ablation in local chondrogenic and/or perichondrial cells. The study indicates that formation of stereotypic exostoses requires a significant, but not complete, loss of Ext expression and that exostosis incidence and phenotype are intimately sensitive to, and inversely related to, Ext expression. The data also indicate that the nature and organization of ectopic tissue may be influenced by site-specific anatomical cues and mechanisms.
Topics: Animals; Cells, Cultured; Exostoses; Fibroblast Growth Factors; Growth Plate; Heparitin Sulfate; Heterozygote; Mice; Mice, Mutant Strains; N-Acetylglucosaminyltransferases; Ribs
PubMed: 21310272
DOI: 10.1016/j.bone.2011.02.001 -
International Journal of Surgery Case... May 2024Multiple Hereditary Exostoses is a rare autosomal dominant bone disorder that predominantly affects males at an incidence of (1:50,000 to 1:100,000) in Western...
INTRODUCTION AND IMPORTANCE
Multiple Hereditary Exostoses is a rare autosomal dominant bone disorder that predominantly affects males at an incidence of (1:50,000 to 1:100,000) in Western populations. The etiology is owed to mutations in the EXT gene group, specifically EXT1 and EXT2 which cause the formation of Osteochondromas. Diagnosis is typically established in childhood. Nevertheless, vascular complications are extremely rare while being potentially fatal. Therefore, timely diagnosis and treatment are vital for such patients.
CASE PRESENTATION
We present the case of a 37-year-old Middle Eastern male with Multiple Hereditary Exostoses who experienced sudden-onset left lower limb pain persisting for a month prior to admission. It was associated with coldness and paresthesia of the ipsilateral lower limb. The presurgical radiological workup uncovered a popliteal pseudoaneurysm subsequent to Multiple Hereditary Exostoses.
CLINICAL DISCUSSION
Through open surgery, the vascular perfusion was successfully restored, and a subsequent supra- to infra-geniculate popliteal artery anastomosis via saphenous vein grafting was done. Furthermore, the Osteochondroma was utterly resected to limit recurrence of another vascular injury. The following histopathological analysis confirmed the diagnosis of an Osteochondroma as a result of MHE.
CONCLUSION
Multiple Hereditary Exostoses is a rare occurrence leading to pseudoaneurysms. This event underscores the need for further documentation to aid in establishing a prompt diagnosis and carrying out suitable interventions. Considering this pathology in a multidisciplinary approach ensures proper treatment. Following a comprehensive literature review, our case stands as the first case in the published literature from our country which emphasizes its value and rarity.
PubMed: 38626641
DOI: 10.1016/j.ijscr.2024.109633 -
Indian Journal of Human Genetics May 2008I report a case of a patient who suffered schizophrenia and multiple exostoses and argue the possible role of EXT gene and nearly chromosomal loci in further genetic...
I report a case of a patient who suffered schizophrenia and multiple exostoses and argue the possible role of EXT gene and nearly chromosomal loci in further genetic investigations related to schizophrenia.
PubMed: 20300296
DOI: 10.4103/0971-6866.44107 -
Bone Oct 2020Multiple osteochondromas is a rare hereditary skeletal disorder, characterized by bony protrusions arising from growth plates on long bones during skeletal development....
IMPORTANCE
Multiple osteochondromas is a rare hereditary skeletal disorder, characterized by bony protrusions arising from growth plates on long bones during skeletal development. The disorder frequently leads to diminished stature, deformities and functional limitations. Understanding of the natural history of multiple osteochondromas and its evolution in children and adolescents is limited.
OBJECTIVE
To provide valuable information on the natural history of multiple osteochondromas, to inform recommendations for treatment and prevent impairments caused by osteochondromas.
DESIGN
This retrospective cohort study in children with multiple osteochondromas includes longitudinal data collected from first to last follow-up visit for patient demographics, and over 36 months for disease evolution.
SETTING
Data were collected from the Registry of Multiple Osteochondromas, which includes data from circa 1200 patients with multiple osteochondromas treated from 2003 to 2017 at IRCCS Istituto Ortopedico Rizzoli in Bologna.
PARTICIPANTS
Patients ≤18 years with multiple osteochondromas, who provided written informed consent and had data for ≥1 12-month follow-up visit.
MAIN OUTCOME(S) AND MEASUREMENT(S)
Demographics, clinical features, incidence of surgeries, and disease evolution (progression or regression) were assessed. Results were summarized using descriptive statistics, annual rates of new clinical features and surgeries, and Kaplan-Meier estimates. Patient height was evaluated following Italian growth charts.
RESULTS
158 patients were included in these analyses. Throughout follow-up, 80.4% of patients developed new osteochondromas, 57.6% developed new deformities, 23.4% developed new functional limitation(s). New osteochondroma(s) were developed by 28.5% patients by Month 12, 39.9% at Month 24, 50% at Month 36. Most new osteochondromas were detected in the younger population; patients aged 0-4 years underwent a significantly higher number of lesions within 12, 24 and 36 months of follow-up. The overall incidence of patients with ≥1 new deformity within 12 months was 17.7%, with incidences decreasing with increasing age (p = .023). In addition, the analyses on height highlight that 13 years is a cut off age for slow growth of the stature (p < .0005). At last follow-up visit, 46.2% of patients had disease progression, while regression (spontaneous and surgical) occurred in 7.6% (p = .007).
CONCLUSIONS AND RELEVANCE
This natural history study reports the main set of clinically relevant data for patients with multiple osteochondromas during skeletal development, providing insight for patient management and development of therapeutic interventions.
Topics: Adolescent; Bone Neoplasms; Child; Cohort Studies; Exostoses, Multiple Hereditary; Humans; Italy; Osteochondroma; Retrospective Studies
PubMed: 32592948
DOI: 10.1016/j.bone.2020.115499