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Metabolic Approaches to the Treatment of Back Pain
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
Carrie Diulus, Patrick Hanaway
Spine providers have long been aware of genetic predisposition to degenerative changes in the spine and resultant axial back pain. Family history is an important part of the clinical evaluation for patients with back pain. Recent research has identified SNPs and other genetic factors associated with spinal degeneration, including: rs1337185 and rs1676486 in COL1A1 and rs162509 in ADAMTS5. COL1A1 is a structural gene expressed in the intervertebral disc and encodes the alpha-1 chain of type XI collagen. ADAMTS-4 and ADAMTS-5 are degradative genes in the metalloprotease family. COL1A1 SP1 (a collagen I SNP), COL9a3 Trp2 and Trp3 (a collagen IX SNP), and VDR TaqI (a vitamin D receptor SNP) correlated with lumbar disc degeneration that is proportional to the number of mutations [7–14]. The science around the genetic factors is in its infancy – family history is an important consideration for risk. Genomic SNPs may highlight predisposition to pain, as well as response to standard therapeutic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids.
Intervertebral Disc
Published in Manoj Ramachandran, Tom Nunn, Basic Orthopaedic Sciences, 2018
Will Aston, Alexander Montgomery, Rajiv Bajekal
The role of genetic predisposition is being increasingly recognized as a risk factor. Patients who are diagnosed with herniated discs before the age of 21 years are four to five times more likely to have a significant family history of disc herniation and similar magnetic resonance imaging (MRI) disc degeneration appearances have been noted in monozygotic twins. Genetic variations exist in the degree of synthesis and breakdown of structural components of the disc. Collagen IX encoding genes (COL9A2, COL9A3), genes encoding type I collagen (COL1A1-Sp1 binding site), Sox 9 (regulates the genes for aggrecan), vitamin D receptor gene and matrix metalloproteinase (MMP)-3 gene are some of those being studied for possible association with disc degeneration.
Genetic disorders, skeletal dysplasias and malformations
Published in Ashley W. Blom, David Warwick, Michael R. Whitehouse, Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Fergal Monsell, Martin Gargan, Deborah Eastwood, James Turner, Ryan Katchky
The most common inheritance pattern is autosomal dominant, but there is a less common and clinically distinct autosomal recessive form. The majority of individuals affected with dominant MED have mutations of the COMP (cartilage oligomeric protein) gene, with approximately 10% presenting with abnormalities of the MATN3 gene, both affecting matrix production and causing abnormalities of the physical and material properties of joint cartilage. Mutations of COL9A1, COL9A2 and COL9A3 are uncommon and cause accumulation of type IX collagen and also lead to abnormalities of articular cartilage.
Streptococcal pyomyositis in asplenia and underlying connective tissue disease
Published in Baylor University Medical Center Proceedings, 2023
John Nguyen, Pardeep Singh, Tapas Gajjar
Stickler syndrome is a connective tissue disease that affects collagen (types II, IX, and XI) in the vitreous, inner ear, and skeleton. Common symptoms of Stickler syndrome include retinal detachment, distinct facies with underdeveloped maxilla, early arthritis along with joint hypermobility that typically resolves in adulthood, sensorineural hearing loss more prevalent with age, and scoliosis.9 The diagnosis of Stickler syndrome is made on clinical symptoms and genetic testing showing abnormal genes associated with collagen formation.10 The more common autosomal dominant Stickler syndrome types involve heterozygous pathogenic variants of COL2A1 (type I) and COL11A1 (type II), and rarer autosomal recessive types involve heterozygous pathogenic variants of COL9A1/COL9A2/COL9A3.10 Some connective tissue diseases such as systemic lupus erythematosus and polymyositis increase infection risk due to impaired immunity or impaired bronchial clearing,8 but no clear infection risk with Stickler syndrome has been described. Additionally, while anti-CCP can be found in 5% to 10% of non–rheumatoid arthritis connective tissue diseases, it has no correlation with Stickler syndrome.11
Severe foveal hypoplasia and macular degeneration in Stickler syndrome caused by missense mutation in COL2A1 gene
Published in Ophthalmic Genetics, 2022
Mamika Asano, Katsuhiko Yokoyama, Kazuma Oku, Itsuka Matsushita, Kenichi Kimoto, Toshiaki Kubota, Hiroyuki Kondo
Mutations in the procollagen genes, COL2A1, COL11A1, COL11A2, COL9A1, COL9A2 and COL9A3 cause Stickler syndrome, and the COL2A1, COL11A1 and COL11A2 genes are responsible for autosomal dominant Stickler syndrome (4). Mutations in the COL2A1 gene are the most common cause of Stickler syndrome, and more than 80% of the mutations are truncation mutations, i.e., nonsense, insertion, deletion, and splicing mutations that lead to haploinsufficiency (Human Gene Mutation Database, HGMD; https://my.qiagendigitalinsights.com/bbp/view/hgmd/pro/start.php). Patients with truncation mutations in the COL2A1 gene show characteristic membranous structures in the vitreous (5,6). On the other hand, some of the missense mutations in the COL2A1 gene have been reported to cause specific alterations of the vitreous due to dominant-negative effects (5). As best we know, there are no reports on whether eyes with missense mutations have specific retinal findings.
Autosomal recessive Stickler syndrome associated with homozygous mutations in the COL9A2 gene
Published in Ophthalmic Genetics, 2021
Ulrika Kjellström, Susanne Martell, Cecilia Brobeck, Sten Andréasson
To this date, few reports have been published on retinal function in Stickler patients. Our study shows reduced function of both rods and cones. These results are in line with findings by Kondo et al. (17) who investigated patients with STL 1. Faletra et al. (13) also reported a Stickler patient with homozygous mutations in the COL9A3 gene, showing ffERG results at the lower limit of normality. Thus, those more recent investigations (13,17), and the present study contradict previous ideas that Stickler patients have normal retinal function unless they are very myopic or have had a retinal detachment (18,19). The proband, e.g. had reduced ffERG parameters although he has only mild myopia. We show both a- and b-wave reduction, indicating that photoreceptors (20) and bipolar cells (21) as well as Müller cells (22) might be involved. The findings of delayed 30 Hz flicker ITs in our study and in the survey by Kondo et al. (17), are somewhat worrying since delayed ITs have been described in progressive disorders, at least in retinal degenerations (23,24). Our measurements also reveal reduced macular function although the gross anatomy on OCT and FAF images is normal. Thus, the reduced BVA in the proband and his brother might be explained, not only by amblyopia due to refractive errors corrected too late but also with retinal dysfunction. In contrast to our normal OCT b-scans, previous studies (17,25) have shown mild foveal hypoplasia in STL 1 patients; thus, the genetic background seems to give somewhat various retinal morphology in Stickler patients.