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Frontiers in Veterinary Science 2020Intervertebral disc disease (IVDD) has been recognized in dogs since the 1800s, when the first descriptions of extruded disc material within the vertebral canal were... (Review)
Review
Intervertebral disc disease (IVDD) has been recognized in dogs since the 1800s, when the first descriptions of extruded disc material within the vertebral canal were published. In the intervening time our understanding of intervertebral disc pathology in dogs and cats has increased dramatically, with many variations of IVDD described. Whilst the volume of literature and collective understanding of IVDD has expanded, there has also been scope for confusion as the definition of intervertebral disc disease, with its myriad different manifestations, becomes more complicated. A large volume of literature has aimed to combine the use of histopathology, diagnostic imaging and clinical findings to better understand the various ways in which IVDD can be classified. Much of this research has focused on the classification of mechanisms of intervertebral disc degeneration, centering around the differences between, and overlaps in, IVDD in chondrodystrophic and non-chondrodystrophic dog breeds. However, with the increasing availability of advanced imaging modalities allowing more accurate antemortem diagnosis, the concept of IVDD has expanded to include other clinical presentations that may not fit into traditional models of classification of IVDD. This review aims to provide an up to date overview of both historical and current systems of IVDD classification, highlighting the important findings and controversies underpinning them.
PubMed: 33134360
DOI: 10.3389/fvets.2020.579025 -
Canadian Medical Association Journal Mar 1912
PubMed: 20310267
DOI: No ID Found -
Communications Biology Mar 2020The Creeper (Cp) chicken is characterized by chondrodystrophy in Cp/+ heterozygotes and embryonic lethality in Cp/Cp homozygotes. However, the genes underlying the...
The Creeper (Cp) chicken is characterized by chondrodystrophy in Cp/+ heterozygotes and embryonic lethality in Cp/Cp homozygotes. However, the genes underlying the phenotypes have not been fully known. Here, we show that a 25 kb deletion on chromosome 7, which contains the Indian hedgehog (IHH) and non-homologous end-joining factor 1 (NHEJ1) genes, is responsible for the Cp trait in Japanese bantam chickens. IHH is essential for chondrocyte maturation and is downregulated in the Cp/+ embryos and completely lost in the Cp/Cp embryos. This indicates that chondrodystrophy is caused by the loss of IHH and that chondrocyte maturation is delayed in Cp/+ heterozygotes. The Cp/Cp homozygotes exhibit impaired DNA double-strand break (DSB) repair due to the loss of NHEJ1, resulting in DSB accumulation in the vascular and nervous systems, which leads to apoptosis and early embryonic death.
Topics: Animals; Apoptosis; Bone Diseases, Developmental; Bone and Bones; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chick Embryo; DNA Repair Enzymes; DNA-Binding Proteins; Embryonic Development; Gene Deletion; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Hedgehog Proteins; Heterozygote; Homozygote; Phenotype; Poultry Diseases
PubMed: 32214226
DOI: 10.1038/s42003-020-0870-z -
Annals of Cardiothoracic Surgery Sep 2016Repair of pectus excavatum began at the beginning of the 20 century before endotracheal intubation was standard practice. Surgeons therefore developed techniques that... (Review)
Review
Repair of pectus excavatum began at the beginning of the 20 century before endotracheal intubation was standard practice. Surgeons therefore developed techniques that corrected the deformity using an open procedure via the anterior chest wall. Initial techniques were unsatisfactory, but by the 1930s the partial rib resection and sternal osteotomy technique had been developed and was used in combination with external traction post-operatively to prevent the sternum from sinking back into the chest. In 1949, Ravitch recommended complete resection of the costal cartilages and complete mobilization of the sternum without external traction, and in 1961 Adkins and Blades introduced the concept of a substernal strut for sternal support. The wide resection resulted in a very rigid anterior chest wall, and in some instances, the development of asphyxiating chondrodystrophy. The primary care physicians therefore became reluctant to refer the patients for repair. In 1987, Nuss developed a minimally invasive technique that required no cartilage or sternal resection and relied only on internal bracing by means of a sub-sternal bar, which is inserted into the chest through two lateral thoracic incisions and guided across the mediastinum with the help of thoracoscopy. After publication of the procedure in 1998, it became widely accepted and a flood of new patients suddenly started to appear, which allowed for rapid improvements and modifications of the technique. New instruments were developed specifically for the procedure, complications were recognized, and the steps taken to prevent them included the development of a stabilizer and the use of pericostal sutures to prevent bar displacement. Various options were developed for sternal elevation prior to mediastinal dissection to prevent injury to the mediastinal structures, allergy testing was implemented, and pain management improved. The increased number of patients coming for repair permitted studies of cardiopulmonary function, which showed that patients with a severe degree of pectus excavatum have right- sided cardiac compression, decreased filling, and decreased stroke volume. The degree of pulmonary restriction and obstruction is related to the degree of deformity and degree of cardiac displacement into the left chest. The indications for surgical repair have been clearly outlined, the procedure has been standardized, and post-operative management protocols are now available. A review of our prospective database showed that 98% of patients have a good to excellent outcome. This review of the "Past" outlines the progression of the surgical techniques during the 20 century, the review of the "Present" outlines the important modifications and results of the closed technique, and the review of the "Future" outlines the various new options that are becoming available for the treatment of pectus excavatum.
PubMed: 27747175
DOI: 10.21037/acs.2016.08.05 -
Drug Design, Development and Therapy 2011Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety... (Review)
Review
Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA) for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS), which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell-Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.
Topics: Body Height; Drug Approval; Growth Disorders; Human Growth Hormone; Humans; United States; United States Food and Drug Administration
PubMed: 21966214
DOI: 10.2147/DDDT.S23140 -
Romanian Journal of Morphology and... 2006Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 gene (4p16), characterized by chondrodystrophy, postaxial...
Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 gene (4p16), characterized by chondrodystrophy, postaxial polydactyly, ectodermal dysplasia and cardiac anomalies. We present the case of a 24 years old female patient with unaffected parents and an affected sister, with a personal history of surgically corrected postaxial polydactyly of both hands and atriventricular canal. Clinical features were: a marked acromesomelic short stature (135 cm height), narrow thorax, genu valgum, club feet, brachydactyly, malposed toes, hypoplastic nails and teeth, diffuse alopecia, atrioventricular canal, hypoplastic mammary glands and a small goiter. Radiologic evaluation revealed short metacarpals and phalanges, capitat and hamat fusion on the left, left ulnar epiphysis with areas of osteolysis and osteocondensation, genu valgum, short fibulae, narrow thorax, cardiac enlargement with hilar congestion. Echocardiogram showed absence of the atrial sept and the basal portion of the ventricular sept and electrochardiogram--right bundle branch block, left anterior fascicular block and left ventricular hypertrophy. Free thyroxine, TSH and usual laboratory parameters were in the normal range with exception of ionic calcium which was low (3.8 mg/dL).
Topics: Adult; Echocardiography; Ellis-Van Creveld Syndrome; Female; Hand; Humans; Radiography, Thoracic
PubMed: 17392984
DOI: No ID Found -
Genes Feb 2022Two retrogenes ( on chromosome 18 and on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both...
Two retrogenes ( on chromosome 18 and on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both retrogenes (e.g., Dachshunds) and others are homozygous for just one (e.g., Beagles and Scottish Terriers). Since most breeds do not segregate both of these retrogenes, it is challenging to evaluate their individual effects on long bone length and body size. We identified two dog breeds selected for hunting ability, the Alpine Dachsbracke and the Schweizer Niederlaufhund, that segregate both of these retrogenes. Using individual measurements of height at the shoulder, back length, head width, thorax depth and width, and thoracic limb measurements, we evaluated the combined effects of retrogenes within these breeds. We applied multivariable linear regression analysis to determine the effects of retrogene copy numbers on the measurements. Copy numbers of both retrogenes had significant effects reducing height at the shoulders and antebrachial length, with having a much greater effect than . alone influenced the degree of carpal valgus and alone increased head width. Neither retrogene had an effect on thorax width or depth. Selectively breeding dogs with and without would likely lead to a reduction in the -related risk of intervertebral disc herniation while maintaining the reduction in leg length resulting from
Topics: Animals; Dogs; Intervertebral Disc Displacement
PubMed: 35205370
DOI: 10.3390/genes13020325 -
Journal of Orthopaedic Research :... Dec 2019Osteoarthritis (OA) is a degenerative joint disease associated with chronic pain and disability in humans and companion animals. The canine species can be subdivided...
Osteoarthritis (OA) is a degenerative joint disease associated with chronic pain and disability in humans and companion animals. The canine species can be subdivided into non-chondrodystrophic (NCD) and chondrodystrophic (CD) dogs, the latter having disproportionally short limbs due to disturbance in endochondral ossification of long bones. This phenotype is associated with retrogene insertions of the fibroblast growth factor 4 (FGF4) gene, resulting in enhanced fibroblast growth factor receptor 3 (FGFR3) signaling. The effect on cartilage is unknown and in experimental studies with dogs, breeds are seemingly employed randomly. The aim of this study was to determine whether CD- and NCD-derived cartilage differs on a structural and biochemical level, and to explore the relationship between FGF4 associated chondrodystrophy and OA. Cartilage explants from CD and NCD dogs were cultured for 21 days. Activation of canonical Wnt signaling was assessed in primary canine chondrocytes. OA and synovitis severity from an experimental OA model were compared between healthy and OA samples from CD and NCD dogs. Release of glycosaminoglycans, DNA content, and cyclooxygenase 2 (COX-2) expression were higher in NCD cartilage explants. Healthy cartilage from NCD dogs displayed higher cartilage degeneration and synovitis scores, which was aggravated by the induction of OA. Dikkopf-3 gene expression was higher in NCD cartilage. No differences in other Wnt pathway read outs were found. To conclude, chondrodystrophy associated with the FGF4 retrogene seems to render CD dogs less susceptible to the development of OA when compared with NCD dogs. These differences should be considered when choosing a canine model to study the pathobiology and new treatment strategies of OA. © 2019 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 37:2550-2560, 2019.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cartilage, Articular; Cyclooxygenase 2; Disease Models, Animal; Dogs; Fibroblast Growth Factor 4; Glycosaminoglycans; Osteoarthritis; Receptor, Fibroblast Growth Factor, Type 3; Wnt Signaling Pathway
PubMed: 31373395
DOI: 10.1002/jor.24432 -
Frontiers in Veterinary Science 2020Premature degeneration of the intervertebral disc and its association with specific chondrodystrophic dog breeds has been recognized for over a century. Several lines of... (Review)
Review
Premature degeneration of the intervertebral disc and its association with specific chondrodystrophic dog breeds has been recognized for over a century. Several lines of evidence including disease breed predisposition, studies suggesting heritability of premature intervertebral disc degeneration (IVDD) and association of a dog chromosome 12 (CFA 12) locus with intervertebral disc calcification have strongly supported a genetic component in IVDD in dogs. Recent studies documenting association of IVDD with an overexpressing retrogene on CFA 12 have opened up new areas of investigation to further define the pathophysiology of premature IVDD. While preliminary data from studies investigating FGF4 retrogenes in IVDD implicate FGF4 overexpression as a major disease factor, they have also highlighted knowledge gaps in our understanding of intervertebral disc herniation which is a complex and multifactorial disease process.
PubMed: 32793650
DOI: 10.3389/fvets.2020.00431 -
Proceedings of the National Academy of... Oct 2017Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide...
Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed ( = 0.01) and intervertebral disc disease (IVDD) across breeds ( = 4.0 × 10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed retrogene within this shared region. The retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.
Topics: Animals; Dog Diseases; Dogs; Fibroblast Growth Factor 4; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Mutagenesis, Insertional; Osteochondrodysplasias
PubMed: 29073074
DOI: 10.1073/pnas.1709082114