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Journal of Clinical Medicine Research Aug 2016We studied an unusual combination of severe short stature, mesomelia (Leri-Weill dyschondrosteosis syndrome), and multiple exostosis in several family subjects over...
BACKGROUND
We studied an unusual combination of severe short stature, mesomelia (Leri-Weill dyschondrosteosis syndrome), and multiple exostosis in several family subjects over three generations. The pattern of inheritance was compatible with autosomal dominant.
METHODS
Of 21 affected members over three generations, shortness of stature, associated with mesomelia resembling Leri-Weill dyschondrosteosis syndrome with no exostoses was evident in three family subjects. The rest of the family subjects manifested with normal height, and yet multiple exostoses. In this family, the skeletal manifestations were sufficiently variable for the presentation to be with either short stature or scoliosis, a Madelung' deformity, or with severe hallux valgus associated with exostosis and with Leri-Weill dyschondrosteosis syndrome.
RESULTS
Subjects with structural chromosomal aberrations of the proband IV-7, who manifested with normal height but with multiple exostoses were excluded via 20 CAG-banded mitoses (there were no microdeletions or microduplication after performing Array-CGH-analysis). In addition, DNA examination for subject IV-8 (male cousin of the proband showed short stature and Leri-Weill dyschondrosteosis syndrome) revealed no evidence of SHOX deletions.
CONCLUSION
We described a multigenerational non-consanguineous North African family , in which mesomelic dysplasia, whose clinical and radiological phenotypes resembled dyschondrosteosis, was a prominent feature in three family subjects. Multiple exostoses were evident in several other family subjects (most were with normal height). We would like to emphasize the variability in the phenotypic expression of multiple exostosis, especially the confusion that might arise when the condition appears both clinically and radiologically to be more complicated, and the overall picture might then be overlapped with one of the other bone dysplasias such as Leri-Weill dyschondrosteosis syndrome.
PubMed: 27429682
DOI: 10.14740/jocmr2593w -
Journal of Orthopaedics Jun 2023Exposure to ionizing radiation in patients with Multiple Hereditary Exostoses (MHE) is inevitable and necessary for the diagnosis and treatment of MHE. Radiation...
BACKGROUND
Exposure to ionizing radiation in patients with Multiple Hereditary Exostoses (MHE) is inevitable and necessary for the diagnosis and treatment of MHE. Radiation exposure has many potentially dangerous consequences, including the increased risk of developing cancer. This is especially concerning in the pediatric patient population since children are more likely to develop adverse effects from radiation than adults. This study aimed to quantify radiation exposure over a five-year period among patients diagnosed with MHE since such information is not currently available in the literature.
METHODS
Diagnostic radiographs, computed tomography (CT) scans, nuclear medicine studies, and intraoperative fluoroscopy exposures were analyzed for radiation exposure in 37 patients diagnosed with MHE between 2015 and 2020.
RESULTS
Thirty-seven patients with MHE underwent 1200 imaging studies, 976 of which were related to MHE and 224 unrelated to MHE. The mean estimated MHE cumulative radiation dose per patient was 5.23 mSv. Radiographs related to MHE contributed the most radiation. Patients from the ages of 10- to 24-years-old received the most imaging studies and exposure to ionizing radiation, especially compared to those under age 10 ( = 0.016). The 37 patients also received a total of 53 surgical-excision procedures, with a mean of 1.4 procedures per person.
CONCLUSIONS
MHE patients are exposed to increased levels of ionizing radiation secondary to serial diagnostic imaging, with those ages 10-24 years old being exposed to significantly higher doses of radiation. Because pediatric patients are more sensitive to radiation exposure and are at an overall higher risk, the use of radiographs should always be justified in those patients.
PubMed: 37234093
DOI: 10.1016/j.jor.2023.05.004 -
Clinics in Orthopedic Surgery Dec 2020Multiple hereditary exostosis is a common autosomal dominant inherited musculoskeletal disorder that manifests with multiple osteochondromas. The clinical manifestations...
BACKGROUND
Multiple hereditary exostosis is a common autosomal dominant inherited musculoskeletal disorder that manifests with multiple osteochondromas. The clinical manifestations and pathological characteristics of osteochondromas found in the long bone and genetic alterations related to multiple hereditary exostosis have been widely reported. In this study, we investigated the characteristics of brachymetacarpia and brachymetatarsia associated with multiple hereditary exostosis.
METHODS
Of the 133 patients with a diagnosis of multiple hereditary exostosis who were recruited from 2005 to 2018, 101 patients who underwent plain radiography after 10 years of age were included. There were 55 male (54.5%) and 46 female (45.5%) patients. Brachymetacarpia or brachymetatarsia was diagnosed when disruption of the Lièvre parabola connecting the metacarpal or metatarsal heads was observed on plain radiographs. Three orthopedic surgeons individually reviewed hand and foot plain radiographs.
RESULTS
Of the 101 patients, 41 patients (40.6%) had more than 1 brachymetacarpia (88 cases) or brachymetatarsia (81 cases). Among 41 cases, 22 (53.7%) were male and 19 (46.3%) were female. The mean age at the time of radiographic evaluation of the hands and feet was 14.6 years (range, 10-63 years). Shortening was most commonly found in the 3rd and 4th metacarpal or metatarsal bones.
CONCLUSIONS
We found a relatively high incidence of brachymetacarpia and brachymetatarsia in our patients. Physicians should suspect the presence of brachymetacarpia and brachymetatarsia when treating patients with multiple hereditary exostosis.
Topics: Adolescent; Adult; Child; Exostoses, Multiple Hereditary; Female; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Male; Middle Aged; Radiography; Young Adult
PubMed: 33274034
DOI: 10.4055/cios19121 -
Brain Sciences Oct 2020Potocki-Shaffer syndrome (PSS) is a rare non-recurrent contiguous gene deletion syndrome involving chromosome 11p11.2. Current literature implies a minimal region with... (Review)
Review
Potocki-Shaffer syndrome (PSS) is a rare non-recurrent contiguous gene deletion syndrome involving chromosome 11p11.2. Current literature implies a minimal region with haploinsufficiency of three genes, (parietal foramina), (multiple exostoses), and (craniofacial anomalies, and intellectual disability). The rest of the PSS phenotype is still not associated with a specific gene. We report a systematic review of the literature and included two novel cases. Because deletions are highly variable in size, we defined three groups of patients considering the PSS-genes involved. We found 23 full PSS cases (, and ), 14 cases with , and three with only. Among the latter, we describe a novel male child showing developmental delay, café-au-lait spots, liner postnatal overgrowth and West-like epileptic encephalopathy. We suggest PSS cases may have epileptic spasms early in life, and is likely to be the causative gene. Given their subtle presentation these may be overlooked and if left untreated could lead to a severe type or deterioration in the developmental plateau. If our hypothesis is correct, a timely therapy may ameliorate PSS phenotype and improve patients' outcomes. Our analysis also shows is a candidate for the overgrowth phenotype.
PubMed: 33126574
DOI: 10.3390/brainsci10110788 -
BMC Musculoskeletal Disorders Feb 2021This study aimed to investigate the characteristic deformities of the hip in multiple hereditary exostoses patients (MHE) and its association with the hip impingement...
BACKGROUNDS
This study aimed to investigate the characteristic deformities of the hip in multiple hereditary exostoses patients (MHE) and its association with the hip impingement syndrome.
MATERIALS AND METHODS
Between 2001 and 2019, total 51 patients (102 hips) were evaluated in this study. Patients with MHE were classified to femoro-acetabular impingement (FAI) symptom group, ischio-femoral impingement (IFI) symptom group and non-impingement symptom group by comparing the symptoms, clinical signs and imaging studies. To assess the morphometry of the hip in patients with MHE, the femoral neck-shaft angle, Sharp's acetabular angle and center-edge (CE) angle were evaluated. Alpha angle was further evaluated to investigate the FAI using radiographs, and the minimum ischio-femoral distance was further measured to investigate the IFI using computed-tomographic (CT) study.
RESULTS
On hip impingement symptom analysis, FAI symptom and IFI symptom were confirmed in 14 hip joints and 18 hip joints, respectively. Unlike general population, the number of the hip with IFI-symptom was higher than those with FAI symptom in this study. In morphometric evaluation of MHE hips, coxa valga was most prominent deformity with occasional tendency of mild acetabular dysplasia. In a comparison of morphometric study between the impingement symptom group and non-symptom group, the FAI symptom showed significant differences of morphometric measure values than those of the non-symptom group (FAI symptom group vs. Non-FAI symptom group; Femoral neck-shaft angle (153.9 vs 142.6), Sharp's angle (45.0 vs 41.5), CE angle (21.1 vs 28.8) and alpha angle (76.7 vs 57.9)). Similarly, the IFI symptom group also showed significant differences of morphometric measure values than those of the non-symptom group (IFI-symptom vs. Non-IFI symptom; Femoral neck-shaft angle (150.9 vs 142.7), Sharp's angle (44.7 vs 41.4), CE angle (21.1 vs 29.3) and alpha angle (73.3 vs 56.8)). In addition, the minimum ischio-femoral distance measured using CT was significantly decreased in the IFI symptom group (IFI symptom group: 6.6, Non-IFI symptom group: 16.4).
CONCLUSION
The results suggest that the characteristic deformities represented by coxa valga in the MHE hip act as an offset for FAI symptoms, on the contrary, act as a trigger for IFI symptoms.
LEVEL OF EVIDENCE
Level III.
Topics: Exostoses, Multiple Hereditary; Femoracetabular Impingement; Hip Dislocation; Hip Dislocation, Congenital; Hip Joint; Humans
PubMed: 33549073
DOI: 10.1186/s12891-021-04021-1 -
PloS One 2017This paper reports a case of multiple osteochondromas affecting the antlers and the left zygomatic bone of a free-ranging adult white-tailed buck (Odocoileus...
This paper reports a case of multiple osteochondromas affecting the antlers and the left zygomatic bone of a free-ranging adult white-tailed buck (Odocoileus virginianus) from Georgia, USA. Along with a few postcranial bones, the antlered cranium of the individual was found in a severely weathered condition and devoid of any soft tissue. The antlers exhibited five pedunculated exostoses that were composed of cancellous bone and, in their peripheral portions, also mineralized cartilage. The largest of the exostoses, located on the right antler, had a maximum circumference of 55 cm. The exostosis arising from the zygomatic bone was broad-based and much smaller than the exophytic outgrowths on the antlers. Diagnosis of the exostoses as osteochondromas was based on their overall morphology, the normal bone structure in their stalk regions, and the continuity of their spongiosa and cortex with the respective components of the parent bones. Antleromas, i.e., pathological outgrowths developing on antlers as a result of insufficient androgen production, were excluded in the differential diagnosis, based on (1) the apparent maturity and, except for the tumors, normal shape of the antlers and (2) the fact that exostosis formation had also affected the zygomatic bone. Previously only a single case of solitary osteochondroma of an antler has been described in the scientific literature. The case presented here is the first report of multiple osteochondromas in a deer. As antlers are regularly collected as trophies, and huge numbers of them are critically inspected each year, the fact that thus far only two cases of antler osteochondromas have been reported suggests that these tumors are very rare.
Topics: Animals; Antlers; Bone Neoplasms; Deer; Osteochondroma; Skull; Tomography, X-Ray Computed
PubMed: 28296944
DOI: 10.1371/journal.pone.0173775 -
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 -
Cureus Jul 2021We describe the case of a 20-year-old man who presented with a bony swelling over the medial proximal tibia that caused pain along the pes anserinus tendons, and a...
We describe the case of a 20-year-old man who presented with a bony swelling over the medial proximal tibia that caused pain along the pes anserinus tendons, and a history of multiple asymptomatic bony swellings. Wide extraperiosteal resection of the swelling relieved the symptoms with a good outcome within a year. This report describes the pictorial pathoanatomy of a relatively rare association of pes anserinus syndrome caused by osteochondroma in an adult patient. Proximal tibial osteochondromas can also present as pes anserinus syndrome in adult patients with diaphyseal aclasis. Large swellings require wide excision to relieve the stretching pain of pes tendons.
PubMed: 34430155
DOI: 10.7759/cureus.16548 -
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 -
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