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Skeletal Radiology Jan 1996A 6-month-old male monkey with rickets was found dead by its keeper. Radiographic studies showed osteopenia of the entire skeletal system, a cup-shaped concavity and... (Review)
Review
A 6-month-old male monkey with rickets was found dead by its keeper. Radiographic studies showed osteopenia of the entire skeletal system, a cup-shaped concavity and poor mineralization of metaphyseal ends, and markedly widened and irregular epiphyseal growth plates of the long bones and ribs. Gross anatomic findings included bowing abnormalities and microfractures in the radius, ulna, tibia, and fibia, and enlarged and widened cartilage columns extending into the metaphyses in the long bones and ribs. Histologic features included deficient mineralization and irregular disordered columns of proliferating cartilage in growth plates extending into other zones, dilated vascular channels, and poor mineralization of chondroid and osteoid tissues.
Topics: Animals; Bone and Bones; Haplorhini; Male; Monkey Diseases; Radiography; Rickets; Vitamin D Deficiency
PubMed: 8717124
DOI: 10.1007/s002560050035 -
Clinical Genetics Nov 1978Two young adults with Pyle disease have been investigated in a large Afrikaner kindred in South Africa. Consanguinity was present in the family, and it is likely that...
Two young adults with Pyle disease have been investigated in a large Afrikaner kindred in South Africa. Consanguinity was present in the family, and it is likely that the condition was inherited as an autosomal recessive. This contention is supported by the radiographic demonstration of minor degrees of widening of the distal femora in obligatory and potentially heterozygous relatives. Apart from genu valgus of moderate degree, the patients enjoyed good health and their gross radiographic skeletal abnormalities contrasted with the innocuous clinical presentation. Differentiation of Pyle disease from the autosomal dominant and autosomal recessive forms of cranio-metaphyseal dysplasia is of prognostic importance in view of the potentially serious complications in these latter disorders.
Topics: Adult; Bone Diseases, Developmental; Consanguinity; Female; Femur; Genes, Recessive; Humans; Male; Pedigree; Radiography; Syndrome
PubMed: 709903
DOI: 10.1111/j.1399-0004.1978.tb02142.x -
The British Journal of Radiology Feb 1988The radiographic appearances are reported of chronic stress to the wrist joints of eight adolescent males, seven gymnasts and one roller skater. These consist of... (Review)
Review
The radiographic appearances are reported of chronic stress to the wrist joints of eight adolescent males, seven gymnasts and one roller skater. These consist of bilateral, asymmetrical widening and irregularity of the distal radial growth plates with an ill-defined cystic appearance, sclerosis and flaring of the metaphyses in all eight cases. Similar but less marked changes were present in the distal ulnar growth plates in five cases. The aetiology is thought to be that of a Salter Type I stress fracture of the growth plate due to chronic repetitive shear forces applied to the hyperextended wrist joint. Rapid healing of the stress fracture will occur with cessation of the sporting activity but continued strenuous use of the wrists will result in further widening and irregularity of the growth plate. The differential diagnosis of the radiographic appearances and previous literature are discussed.
Topics: Adolescent; Athletic Injuries; Cumulative Trauma Disorders; Follow-Up Studies; Fractures, Bone; Gymnastics; Humans; Male; Radiography; Skating; Wrist Injuries
PubMed: 3280066
DOI: 10.1259/0007-1285-61-722-109 -
Journal of Medical Genetics Aug 2023Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen....
BACKGROUND
Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to present a novel OI phenotype and its causative candidate gene.
METHODS
Whole-exome sequencing and clinical evaluation were performed in five patients from two unrelated families. mRNA expression in blood and fibroblasts was investigated by real-time PCR, and western blot analysis was further performed on skin fibroblasts.
RESULTS
The common findings among the five affected children were recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. We identified biallelic NM_001144758.3:c.2392dup and NM_001144758.3:c.2690_2693del pathogenic variants in in the affected patients, respectively, in the families; parents were heterozygous for these variants. encodes pleckstrin homology-like domain family B member-1 (PHLDB1) protein, which has a role in insulin-dependent Akt phosphorylation. Compared with controls, a decrease in the expression levels of in the blood and skin fibroblast samples was detected. Western blot analysis of cultured fibroblasts further confirmed the loss of PHLDB1.
CONCLUSION
Two biallelic frameshift variants in the candidate gene were identified in independent families with a novel, mild-type, autosomal recessive OI. The demonstration of decreased mRNA expression levels in blood and fibroblast samples supports the hypothesis that pathogenic variants are causative for the observed phenotype.
Topics: Humans; Child, Preschool; Osteogenesis Imperfecta; Heterozygote; Phenotype; Frameshift Mutation; Fractures, Bone; Collagen Type I; Mutation; Nerve Tissue Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 36543534
DOI: 10.1136/jmg-2022-108763 -
Pediatric Radiology Jan 2000Pyle's disease is a rare skeletal dysplasia involving the metaphyses of long bones. To date, spinal involvement has been only rarely described in the literature.
BACKGROUND
Pyle's disease is a rare skeletal dysplasia involving the metaphyses of long bones. To date, spinal involvement has been only rarely described in the literature.
OBJECTIVE
To show that spinal changes, which are an expression of the same growth defect of the long bones, are an important and constant sign of the disease in the families studied.
MATERIALS AND METHOD
The radiographic skeletal changes in five patients have been observed.
RESULTS
The pathognomonic metaphyseal widening of tubular bones (known as the 'Erlenmeyer flask sign') was associated with the spinal changes in all cases. Radiographic findings in the spine varied from moderate platyspondyly to the bodies having the appearance of a biconcave lens. This may be attributed to two main causes: (1) a defect in the modelling process of the vertebrae (comparable to that observed in the metaphyses) and (2) chronic pathological fractures secondary to osteoporosis (a typical feature of Pyle's disease).
CONCLUSIONS
The finding of platyspondyly of varying severity widens the spectrum of radiographic findings in this disease and can assist in diagnosis.
Topics: Adolescent; Adult; Bone Diseases, Developmental; Child; Female; Humans; Male; Middle Aged; Radiography; Spinal Diseases; Spine; Tibia
PubMed: 10663503
DOI: 10.1007/s002470050006 -
American Journal of Medical Genetics Jun 2001We describe a new autosomal dominant type of metaphyseal dysplasia (MD) in five generations of a German kindred. The main characteristics are metaphyseal widening and...
We describe a new autosomal dominant type of metaphyseal dysplasia (MD) in five generations of a German kindred. The main characteristics are metaphyseal widening and undermodeling of the tubular bones with Erlenmeyer flask-like appearance of the distal femora (typical of MD), with unusually severe varus deformity of the radii and flat exostoses of the long bones localized in the metaphyses. The skull is unaffected. Allelism with craniometaphyseal dysplasia (CMD) was excluded by linkage analysis.
Topics: Child; Exostoses, Multiple Hereditary; Female; Femur; Genes, Dominant; Genetic Linkage; Germany; Humans; Male; Osteochondrodysplasias; Pedigree; Radiography; Radius
PubMed: 11343343
DOI: 10.1002/ajmg.1317 -
American Journal of Medical Genetics.... Jul 2021Dysosteosclerosis is a group of sclerosing bone dysplasia characterized by short stature, increased bone fragility, osteosclerosis, and platyspondyly. It is a...
Dysosteosclerosis is a group of sclerosing bone dysplasia characterized by short stature, increased bone fragility, osteosclerosis, and platyspondyly. It is a genetically heterogeneous disorder caused by biallelic mutations in the SLC29A3, TNFRSF11A, TCIRG1, and CSF1R genes. To date, four dysosteosclerosis patients with SLC29A3 mutations have been reported. Here, we report biallelic SLC29A3 (c.303_320dupCTACTTTGAGAGCTACCT) variant in a three-year-old girl. She had large anterior fontanelle, fracture history, short stature, camptodactyly, elbow contracture, and melanocytic nevus. Initial skeletal radiographs revealed platyspondyly, dense vertebral endplates (sandwich appearance of the vertebral bodies), diffuse sclerosis of the peripheral side of the pelvic bones, sclerosis of metaphysis and diaphysis of the long bones, metaphyseal widening, and diaphyseal cortical thickening. Mild sclerosis was also present in the skull base, maxilla, rib, scapula, and phalanges. Notably, we observed that sandwich vertebrae appearance significantly resolved and sclerosis of ribs, scapula, pelvis, and long bone metaphysis regressed over a 2.5-year period. However, platyspondyly, metaphyseal widening, and diaphyseal cortical thickening persisted. In conclusion, this study demonstrates spontaneous resolution of osteosclerosis, which was not described previously in patients with dysosteosclerosis.
Topics: Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Mutation; Nucleoside Transport Proteins; Osteosclerosis; Ribs; Spine; Turkey
PubMed: 33837634
DOI: 10.1002/ajmg.a.62198 -
PloS One 2014Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via...
Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the α1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth.
Topics: Animals; Biomechanical Phenomena; Bone and Bones; Cartilage; Epiphyses; Extracellular Matrix Proteins; Femur; Gene Silencing; Growth Plate; Integrin-Binding Sialoprotein; Mice; Osteopontin; Phenotype; Proteome; RNA, Messenger; X-Ray Microtomography
PubMed: 23755099
DOI: 10.1371/journal.pone.0063080 -
Acta Ortopedica Brasileira 2022Many experimental models exist to better understand the necrosis of the femoral head etiology, both in terms of the species variety in which necrosis is induced and in...
UNLABELLED
Many experimental models exist to better understand the necrosis of the femoral head etiology, both in terms of the species variety in which necrosis is induced and in the operative techniques used for treatment.
OBJECTIVE
This study has two main objectives, the first is to review the literature concerning experimental models of avascular necrosis of the growing femoral head, the second, to demonstrate the experimental pig model's reproducibility using a pilot study.
METHODS
This was a bibliographic review to describe the attempts over time to find the best species and technique for induction that would reproduce ischemic necrosis of the growing femoral head in humans. Simultaneously, a pilot study was performed to verify the replication of induction in pigs, the species that has more similarities with the human hip. The pilot's methodological analysis consists of conventional radiology and verification of possible anatomical, pathological changes.
RESULTS
In imaging exams; lateral sub-dislocation of the femur head and triangular appearance of the head were observed, characterizing its flattening; in macroscopic examination, the femoral head flattening with femoral neck widening and shortening was identified; in histology, the proliferation of articular cartilage with the presence of vascular granulation regenerative tissue, with osteoclasts and fibrocartilaginous tissue in the metaphyseal femoral neck region was identified.
CONCLUSION
The experimental pig model can be used as a valuable tool for the reproducibility of anatomical, pathological changes in ischemic necrosis of the growing femoral head. The model is reproducible and feasible and can be beneficial for future studies on the anatomical pathology of necrosis of the growing femoral head. .
PubMed: 35719181
DOI: 10.1590/1413-785220223002247996 -
Scientific Reports Oct 2018Mutations in the progressive ankylosis protein (NP_473368, human ANKH) cause craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial...
Mutations in the progressive ankylosis protein (NP_473368, human ANKH) cause craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and widened metaphyses in long bones. The pathogenesis of CMD remains largely unknown, and treatment for CMD is limited to surgical intervention. We have reported that knock-in mice (Ank) carrying a F377del mutation in ANK (NM_020332, mouse ANK) replicate many features of CMD. Interestingly, ablation of the Ank gene in Ank mice also leads to several CMD-like phenotypes. Mutations causing CMD led to decreased steady-state levels of ANK/ANKH protein due to rapid degradation. While wild type (wt) ANK was mostly associated with plasma membranes, endoplasmic reticulum (ER), Golgi apparatus and lysosomes, CMD-linked mutant ANK was aberrantly localized in cytoplasm. Inhibitors of proteasomal degradation significantly restored levels of overexpressed mutant ANK, whereas endogenous CMD-mutant ANK/ANKH levels were more strongly increased by inhibitors of lysosomal degradation. However, these inhibitors do not correct the mislocalization of mutant ANK. Co-expressing wt and CMD-mutant ANK in cells showed that CMD-mutant ANK does not negatively affect wt ANK expression and localization, and vice versa. In conclusion, our finding that CMD mutant ANK/ANKH protein is short-lived and mislocalized in cells may be part of the CMD pathogenesis.
Topics: Animals; Bone Diseases, Developmental; Cells, Cultured; Craniofacial Abnormalities; Humans; Hyperostosis; Hypertelorism; Mice; Mutation; Phosphate Transport Proteins; Proteasome Endopeptidase Complex; Protein Stability; Rats; Saccharomyces cerevisiae; Ubiquitination
PubMed: 30356088
DOI: 10.1038/s41598-018-34157-5