Evaluation of the relationship between canine weight gain from 6 to 15 weeks of age and passive coxofemoral joint (CFJ) laxity at 16 weeks of age.
Longitudinal cohort study.
Full- or half-sibling hounds (n = 56).
Hounds were weighed weekly from 6 to 15 weeks of age. Individual average daily gain (ADG) was calculated for each week (weekly) and for the study (overall). PennHIP distraction index (DI) was determined for each CFJ at 16 weeks. Mixed effects linear models were evaluated for associations of DI (highest and mean) with 15-week weight and ADGs (actual or normalized). Left and right DIs were compared with a Student’s paired t-test. Significance was set at P < .05. Trends were considered at P < .10.
Mean (± SD) 16-week DI score and 15-week weight was 0.67 ± 0.16 and 12.5 ± 1.8 kg, respectively. Within animal left and right DIs were not significantly different. There were no significant associations between DI and any of the weight gains evaluated. There was a trend for a negative relationship between normalized 14-week ADG and DI in one statistical model.
Weight gain from 6 to 15 weeks of age was unrelated to 16-week PennHIP DI in a homogenous canine population with moderate-to-severe CFJ joint laxity.
Based on our results, ad libitum feeding between 6 and 15 weeks of age does not appear to have an adverse impact on joint laxity at 16 weeks of age as measured by the PennHIP DI.
To characterize ground reaction forces (GRFs) and determine whether there were correlations between forces and passive coxofemoral joint laxity in puppies.
Fifty-one 16-week-old hound-breed dogs.
Force-plate gait evaluation and distraction radiographic imaging were performed. Ground reaction forces evaluated included x (mediolateral), y (craniocaudal breaking and propulsion), and z (vertical) peak force and impulse. Z-plane limb loading and unloading rates, loading interval, and weight distribution and y-plane stance time breaking and propulsion percentages were calculated. One-way ANOVA with the Duncan multiple range test was used to evaluate differences in gait variables among limbs. The relationships of left, right, highest, and mean distraction index (DI) with individual limb data of each dog were evaluated with the Spearman rank correlation. Left and right DIs were compared by means of linear regression analysis.
Mean ± SEM DI was 0.67 ± 0.02. Left and right DIs were strongly correlated, but there were no significant relationships between DIs and gait variables. Most fore- and hind limb gait variables differed significantly, whereas paired fore- and hind limb gait variables did not. Asymmetry was most pronounced in the x- and y-planes.
Conclusions and Clinical Relevance
GRFs were consistent with those of clinically normal mature dogs, supporting an absence of association between GRF and DI in young dogs. The GRFs and elucidation of the relationship between GRFs and DI may be useful for future studies in immature dogs.
Canine hip dysplasia (CHD) is characterized by a malformation of the hip joint that leads to joint laxity and consequential degenerative joint disease. The most widely used method for diagnosis of CHD is the ventrodorsal hip-extended radiologic view, commonly referred to as the Orthopedic Foundation for Animals (OFA) method. The method of the University of Pennsylvania Hip Improvement Program (PennHIP), an alternative technique that is based on hip joint laxity, provides a quantitative assessment, the distraction index (DI), of the likelihood of the development of CHD because of increased laxity in the hip joint. Linear regression analysis showed that, across many breeds of dog, the incidence of CHD, as defined by the OFA, is positively correlated with the mean DI, the determination coefficient (r2) being 26%. We used families of Boykin spaniels (BSs) to determine the level of joint laxity in the breed and to conduct an initial whole-genome screening to identify markers that co-segregate with increased joint laxity. Although there was a positive correlation between the incidence of hip dysplasia and increased joint laxity, we did not find significant linkage in the 28 BSs that underwent genotyping, likely owing to the small size of the pedigree.
Femoral geometry and body size are both characterized by substantial heritability. The purpose of this study was to discern whether hip geometry and body size (height and body mass index, BMI) share quantitative trait loci (QTL). Dual-energy X-ray absorptiometric scans of the proximal femur from 1,473 members in 323 pedigrees (ages 31–96 years) from the Framingham Osteoporosis Study were studied. We measured femoral neck length, neck-shaft angle, subperiosteal width (outer diameter), cross-sectional bone area, and section modulus, at the narrowest section of the femoral neck (NN), intertrochanteric (IT), and femoral shaft (S) regions. In variance component analyses, genetic correlations (ρG) between hip geometry traits and height ranged 0.30–0.59 and between hip geometry and BMI ranged 0.11–0.47. In a genomewide linkage scan with 636 markers, we obtained nominally suggestive linkages (bivariate LOD scores ≥ 1.9) for geometric traits and either height or BMI at several chromosomes (4, 6, 9, 15, and 21). Two loci, on chr. 2 (80 cM, BMI/shaft section modulus) and chr. X (height/shaft outer diameter), yielded bivariate LOD scores ≥ 3.0; although these loci were linked in univariate analyses with a geometric trait, neither was linked with either height or BMI. In conclusion, substantial genetic correlations were found between the femoral geometric traits, height and BMI. Linkage signals from bivariate linkage analyses of bone geometric indices and body size were similar to those obtained in univariate linkage analyses of femoral geometric traits, suggesting that most of the detected QTL primarily influence geometry of the hip.
Proximal femoral geometry; Body size; Heritability; Bivariate linkage analysis; Quantitative trait locus
Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1–2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a ‘breeding value’ that could improve the accuracy of predicting a dog’s hip conformation.
Canine hip dysplasia; Genome wide screen; Microsatellites; Single nucleotide polymorphisms (SNP); Breeding values
To establish a predictive method using whole genome genotyping for early intervention in canine hip dysplasia (CHD) risk management, for the prevention of the progression of secondary osteoarthritis (OA), and for selective breeding.
Two sets of dogs (6 breeds) were genotyped with dense SNPs covering the entire canine genome. The first set contained 359 dogs upon which a predictive formula for genomic breeding value (GBV) was derived by using their estimated breeding value (EBV) of the Norberg angle (a measure of CHD) and their genotypes. To investigate how well the formula would work for an individual dog with genotype only (without using EBV or phenotype), a cross validation was performed by masking the EBV of one dog at a time. The genomic data and the EBV of the remaining dogs were used to predict the GBV for the single dog that was left out. The second set of dogs included 38 new Labrador retriever dogs, which had no pedigree relationship to the dogs in the first set.
The cross validation showed a strong correlation (r>0.7) between the EBV and the GBV. The independent validation showed a strong correlation (r=0.5) between GBV for the Norberg angle and the observed Norberg angle (no EBV was available for the new 38 dogs). Sensitivity, specificity, positive, and negative predictive value of the genomic data were all above 70%.
Prediction of CHD from genomic data is feasible, and can be applied for risk management of CHD and early selection for genetic improvement to reduce the prevalence of CHD in breeding programs. The prediction can be implemented before maturity, at which age current radiographic screening programs are traditionally applied, and as soon as DNA is available.
Bone mineral density (BMD) is a heritable trait, and in mice, over 100 quantitative trait loci (QTLs) have been reported, but candidate genes have been identified for only a small percentage. Persistent errors in the mouse genetic map have negatively affected QTL localization, spurring the development of a new, corrected map. In this study, QTLs for BMD were remapped in 11 archival mouse data sets using this new genetic map. Since these QTLs all were mapped in a comparable way, direct comparisons of QTLs for concordance would be valid. We then compared human genome-wide association study (GWAS) BMD loci with the mouse QTLs. We found that 26 of the 28 human GWAS loci examined were located within the confidence interval of a mouse QTL. Furthermore, 14 of the GWAS loci mapped to within 3 cM of a mouse QTL peak. Lastly, we demonstrated that these newly remapped mouse QTLs can substantiate a candidate gene for a human GWAS locus, for which the peak single-nucleotide polymorphism (SNP) fell in an intergenic region. Specifically, we suggest that MEF2C (human chromosome 5, mouse chromosome 13) should be considered a candidate gene for the genetic regulation of BMD. In conclusion, use of the new mouse genetic map has improved the localization of mouse BMD QTLs, and these remapped QTLs show high concordance with human GWAS loci. We believe that this is an opportune time for a renewed effort by the genetics community to identify the causal variants regulating BMD using a synergistic mouse-human approach. © 2010 American Society for Bone and Mineral Research.
genetic linkage; quantitative trait loci; mouse; human
Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2
SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis.
association; canine; disease; longevity; morphology; QTL
In patients with structural idiopathic scoliosis the body asymmetries involve the pelvis and the lower limbs; they are included in many theories debating the pathogenesis of idiopathic scoliosis.
Hip joint range of motion was studied in 158 adolescent girls, aged 10–18 years (mean 14.2 ± 2.0) with structural idiopathic scoliosis of 20–83° of Cobb angle (mean 43.0° ± 14.5°) and compared to 57 controls, sex and age matched. Hip range of rotation was examined in prone position, the pelvis level controlled with an inclinometer; hip adduction was tested in five different positions.
In girls with structural scoliosis the symmetry of hip rotation was less frequent (p = 0.0047), the difference between left and right hip range of internal rotation was significantly higher (p = 0.0013), and the static rotational offset of the pelvis, calculated from the mid-points of rotation, revealed significantly greater (p = 0.0092) than in healthy controls. The detected asymmetries comprised no limitation of hip range of motion, but a transposition of the sector of motion, mainly towards internal rotation in one hip and external rotation in the opposite hip. The data failed to demonstrate the curve type, the Cobb angle, the angle of trunk rotation or the curve progression factor to be related to the hip joint asymmetrical range of motion.
Numerous asymmetries around the hip were detected, most of them were expressed equally in scoliotics and in controls. Pathogenic implications concern producing a "torsional offset" of muscles patterns of activation around the spine in adolescent girls with structural idiopathic scoliosis during gait.
A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific.
aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL).
A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosome 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific.
This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to spine and five were linked to hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.
men; sex- specific QTL; genome-wide scan; linkage
Teat number is an important fertility trait for pig production, reflecting the mothering ability of sows. It is also a discrete and often canalized trait presenting bilateral symmetry with minor differences between the two sides, providing a potential power to evaluate fluctuating asymmetry and developmental instability. The knowledge of its genetic control is still limited. In this study, a genome-wide scan was performed with 183 microsatellites covering the pig genome to identify quantitative trait loci (QTL) for three traits related to teat number including the total teat number (TTN), the teat number at the left (LTN) and right (RTN) sides in a large scale White Duroc × Erhualian resource population.
A sex-average linkage map with a total length of 2350.3 cM and an average marker interval of 12.84 cM was constructed. Eleven genome-wide significant QTL for TTN were detected on 8 autosomes including pig chromosomes (SSC) 1, 3, 4, 5, 6, 7, 8 and 12. Six suggestive QTL for this trait were detected on SSC6, 9, 13, 14 and 16. Eight chromosomal regions each on SSC1, 3, 4, 5, 6, 7, 8 and 12 showed significant associations with LTN. These regions were also evidenced as significant QTL for RTN except for those on SSC6 and SSC8. The most significant QTL for the 3 traits were all located on SSC7. Erhualian alleles at most of the identified QTL had positive additive effects except for three QTL on SSC1 and SSC7, at which White Duroc alleles increased teat numbers. On SSC1, 6, 9, 13 and 16, significant dominance effects were observed on TTN, and predominant imprinting effect on TTN was only detected on SSC12.
The results not only confirmed the QTL regions from previous experiments, but also identified five new QTL for the total teat number in swine. Minor differences between the QTL regions responsible for LTN and RTN were validated. Further fine mapping should be focused on consistently identified regions with small confidence intervals, such as those on SSC1, SSC7 and SSC12.
BACKGROUND—To be certain that the joint space width is abnormal in the case of hip joint pain when compared with the contralateral hip requires knowledge of physiological dissymmetry.
AIM OF THE STUDY—To assess interindividual variability and dissymmetry in pelvic radiological joint space width.
METHODS—Pelvic radiographs of subjects without hip joint disease. Measurement with a 0.1 mm graduated magnifying glass and 0.5 mm graduated flat ruler at the hip superointermediate site (vertical going through the femoral head centre). After randomisation of the side to measure, analysis of nine groups of 19 plain films by one investigator blind for the result of the contralateral side.
RESULTS—The difference between the left and right hip was plotted against the corresponding mean for all 171 normal subjects This shows the frequency and the limits of the asymmetry at each measurement site. The asymmetry is independent of interindividual variability of the joint space width and greater than the measurement error in most subjects.
CONCLUSION—This study confirms the interindividual variability of hip joint space width, shows the frequency of hip joint space asymmetry and defines its limit.
Keywords: hip joint; joint space width; measurement
Identification of the genetic basis of common traits may be hindered by underlying complex genetic architectures that are inadequately captured by existing models, including both multiallelic and multilocus modes of inheritance (MOI). One useful approach for localizing genes underlying continuous complex traits is the joint oligogenic linkage and segregation analysis implemented in the package Loki. The method uses reversible jump Markov chain Monte Carlo to eliminate the need to prespecify the number of quantitative trait loci (QTLs) in the trait model, thus providing posterior distributions for the number of QTLs in a Bayesian framework. The current implementation assumes QTLs are diallelic, and therefore can overestimate the number of linked QTLs in the presence of a multiallelic QTL. To address the possibility of multiple alleles, we extended the QTL model to allow for a variable number of additive alleles at each locus. Application to simulated data shows that, under a diallelic MOI, the multiallelic and diallelic analysis models give similar results. Under a multiallelic MOI, the multiallelic analysis model provides better mixing and improved convergence, and leads to a more accurate estimate of the underlying trait MOI and model parameter values, than does the diallelic model. Application to real data shows the multiallelic model results in fewer estimated linked QTLs and that the predominant QTL model is similar to one of two predominant models estimated from the diallelic analysis. Our results indicate that use of a multiallelic analysis model can lead to better understanding of the genetic architecture underlying complex traits.
complex trait; MCMC; pedigree; continuous trait; Bayesian
Background. Local plexiform neurofibroma can lead to deformity of the pelvis, valgus deformity of femoral neck, and joint capsule laxity. We report a case of secondary hip osteoarthritis with subluxation and coxa vara deformity resulting from an extra-articular neurofibroma treated with total hip replacement. Case Description. A 39-year-old man had a large benign plexiform neurofibroma at buttock which induced secondary osteoarthritis of the hip. Conservative treatment of tumor was selected because the patient had low chance of malignant transformation due to absence of other neurofibromatosis features. However, due to secondary osteoarthritis he underwent total hip arthroplasty. Anterior capsulotomy was selected to avoid large posterior hip tumor mass. In order to avoid the difficulties associated with setting tension of the abductor muscle, modified trochanteric slide osteotomy with trochanteric advancement, lateralized cup placement, and extended neck offset were used. One year after the surgery, the patient had excellent clinical function, hip stability, leg length equality and was satisfied with the outcome. Clinical Relevance. We concluded that the modified trochanteric slide osteotomy with trochanteric advancement represents a valuable approach for THR in patients with extremely elongation of the hip abductor and secondary hip osteoarthritis resulting from extra-articular neurofibroma.
We report on a 12 year old mentally retarded boy who presented at birth with bilateral knee dislocations, dislocation of the right hip, and general joint laxity. Cytogenetic studies showed a 49,XXXXY karyotype. Hyperlaxity of joints is known to occur in 49,XXXXY patients, but congenital knee dislocation has not been reported. Rarely in 49,XXXXY and 49,XXXXX syndromes Larsen-like features may be seen. Patients with congenital joint dislocation or laxity, combined with other malformations, especially if psychomotor development is delayed, should be karyotyped to exclude chromosomal abnormalities.
Hip dysplasia is a common developmental problem affecting the canine population. Despite extensive research into the condition, many questions remain unanswered and numerous misconceptions are present among the general public. The purpose of this paper is to review the current knowledge on the development of hip dysplasia, factors modifying its development, and current diagnostic techniques. A computerized literature search was conducted for the period of January 1983 to April 1985 using the MEDLINE and CAB databases, and the keywords hip dysplasia, hip, dog, and canine. Other articles, wherever possible original research articles, published before 1983 were also reviewed. Animals affected by hip dysplasia are born with normal hips, but quickly develop subluxation of the femoral head. Degenerative joint disease follows. Hip dysplasia is a complex, inherited, polygenic trait. Selective breeding of only normal dogs with normal littermates, parents, and grandparents is the recommended method of reducing the incidence in the general population. Gene expression in affected individuals may be modified by a number of environmental factors. These factors do not cause hip dysplasia, but they alter manifestations of the trait and its severity. Nutrition is a major environmental factor. Excess energy consumption increases the frequency and severity of hip dysplasia in genetically predisposed dogs. Food intake should be regulated to maintain a slender figure with the ribs and dorsal vertebral spines easily palpable, but not visible. Excess dietary calcium and vitamin D contribute to hip dysplasia in genetically predisposed individuals and should be avoided. High dose vitamin C supplementation in growing puppies does not prevent hip dysplasia, and this practice should be discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate and characterise an inborn error of metabolism in a dog with skeletal and ocular abnormalities.
A 2.5-year-old small male Miniature Poodle-like dog was presented with gross joint laxity and bilateral corneal opacities. Clinical examination was augmented by routine haematology, serum chemistry, radiographs, pathology, enzymology and molecular genetic studies. Euthanasia was requested when the dog was 3 years of age because of progressively decreasing quality of life.
Radiology revealed generalised epiphyseal dysplasia, malformed vertebral bodies, luxation/subluxation of appendicular and lumbosacral joints with hypoplasia of the odontoid process and hyoid apparatus. These clinical and radiographic findings, together with a positive urinary Berry spot test for mucopolysaccharides, and metachromatic granules in leucocytes, were indicative of a mucopolysaccharidosis (MPS), a lysosomal storage disease. Histological lesions included vacuolation of stromal cells of the cornea, fibroblasts, chondrocytes, macrophages and renal cells. The brain was essentially normal except for moderate secondary Wallerian-type degeneration in motor and sensory tracts of the hind brain. Dermatan sulphateuria was present and enzymology revealed negligible activity of N-acetylgalactosamine-4-sulphatase, also known as arylsulphatase B, in cultured fibroblasts and liver tissue. A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme’s gene was identified (c.103_124del), which caused a frame-shift and subsequent premature stop codon. The “Wisdom pure breed-mixed breed” test reported the dog as a cross between a Miniature and Toy Poodle.
The clinicopathological features are similar to those of MPS type VI as previously described in dogs, cats and other species, and this clinical diagnosis was confirmed by enzymology and molecular genetic studies. This is an autosomal recessively inherited lysosomal storage disease.
The prevalence of MPS VI in Miniature or Toy Poodles in New Zealand and elsewhere is currently unknown. Due to the congenital nature of the disorder, malformed pups may be subject to euthanasia without investigation and the potential genetic problem in the breed may not be fully recognised. The establishment of a molecular genetic test now permits screening for this mutation as a basis to an informed breeding policy.
Lysosomal storage disease; mucopolysaccharidosis; Arylsulphatase B; Miniature/Toy Poodle; mutation
This article discusses the treatment approaches and recommendations for canine hip dysplasia. A search of the literature database MEDLINE (1969-1994) was conducted and relevant journal articles regarding the medical and surgical treatment of hip dysplasia were selected and reviewed. Dysplastic dogs can be divided, for treatment purposes, into those with no or minimal osteoarthrosis, and those with moderate to severe osteoarthrosis. In young animals with joint laxity and pain, but with no or minimal radiographic evidence of osteoarthrosis, the treatment approach is controversial. Conservative management may be effective in the short term, but progressive development of osteoarthrosis occurs and clinical signs may manifest at an older age. Options for surgical treatments in these young dogs include pectineal myectomy, lengthening of the femoral neck, and corrective osteotomies. Corrective osteotomies are advocated to reestablish joint congruency and prevent development of osteoarthrosis. In the mature osteoarthritic dog, effective conservative management depends on the severity of the degenerative joint disease. Proposed surgical treatments for clinically debilitating hip dysplasia include biocompatible osteoconductive/shelf arthroplasty; femoral head and neck excision arthroplasty, with or without muscle sling interposition; and total hip replacement. Although research directly comparing the salvage procedures has not been reported, studies suggest that total hip replacement is more effective in returning large dogs to full functional weight bearing.
Milk composition traits exhibit a complex genetic architecture with a small number of major quantitative trait loci (QTL) explaining a large fraction of the genetic variation and numerous QTL with minor effects. In order to identify QTL for milk fat percentage (FP) in the German Holstein-Friesian (HF) population, a genome-wide association study (GWAS) was performed. The study population consisted of 2327 progeny-tested bulls. Genotypes were available for 44,280 SNPs. Phenotypes in the form of estimated breeding values (EBVs) for FP were used as highly heritable traits. A variance components-based approach was used to account for population stratification. The GWAS identified four major QTL regions explaining 46.18% of the FP EBV variance. Besides two previously known FP QTL on BTA14 (P = 8.91×10−198) and BTA20 (P = 7.03×10−12) within DGAT1 and GHR, respectively, we uncovered two additional QTL regions on BTA5 (P = 2.00×10−13) and BTA27 (P = 9.83×10−5) encompassing EPS8 and GPAT4, respectively. EPS8 and GPAT4 are involved in lipid metabolism in mammals. Re-sequencing of EPS8 and GPAT4 revealed 50 polymorphisms. Genotypes for five of them were inferred for the entire study population. Two polymorphisms affecting potential transcription factor binding sites of EPS8 (P = 1.40×10−12) and GPAT4 (P = 5.18×10−5), respectively, were highly significantly associated with the FP EBV. Our results provide evidence that alteration of regulatory sites is an important aspect of genetic variation of complex traits in cattle.
Context. MEN 2B syndrome is characterized by the presence of medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid features, and skeletal abnormalities like kyphoscoliosis, joint laxity, pes cavus, and slipped capital femoral epiphysis (SCFE) in a minority; we present the case of a young female who was brought to medical attention due to painful hip because of SCFE. Case Report. A 16-year-old female presented to orthopedics out-patient department (OPD) with complaints of pain around the left hip and walking with a limp for the last two months. MRI of hip confirmed the presence of SCFE of the left hip. General examination detected thyroid swelling which was found to be a medullary thyroid cancer and imaging of abdomen confirmed the presence of bilateral pheochromocytoma, also present were neuromas of tongue and lips. Thus, a diagnosis of MEN 2B syndrome was made. Conclusion. SCFE can sometimes be the presenting feature of MEN 2B syndrome. Physicians should keep this in mind as it can lead to early diagnosis of a potentially lethal illness.
Generalized joint laxity is a genetically determined component of overall joint flexibility. The incidence of joint laxity in the overall population is approximately 5% to 20%, and its prevalence is higher in females. Recently it was noticed that individuals with generalized joint laxity are not only prone to anterior cruciate ligament injuries but also have inferior results after a reconstruction. Therefore, an anterior cruciate ligament reconstruction in patients with generalized laxity should be undertaken with caution due to the higher expected failure rate from the complexity of problems associated with this condition. It is also necessary to identify the risk factors for the injury as well as for the post operative outcome in this population. A criterion that includes all the associated components is necessary for the proper screening of individuals for generalized joint laxity. Graft selection for an anterior cruciate reconstruction in patients with ligament laxity is a challenge. According to the senior author, a hamstring autograft is an inferior choice and a double bundle reconstruction with a quadriceps tendon-bone autograft yields better results than a single bundle bone-patella tendon-bone autograft. Future studies comparing the different grafts available might be needed to determine the preferred graft for this subset of patients. Improved results after an anterior cruciate ligament reconstruction can be achieved by proper planning and careful attention to each step beginning from the clinical examination to the postoperative rehabilitation.
Anterior cruciate ligament; Reconstruction; Joint instability; Generalized
Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, ~30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2–2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in other tetrapod taxa.
To examine the relationships between anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) with sagittal plane energetics in males and females during a drop jump task.
A total of 68 females and 50 males were measured for AKL, GR, and GJL and were instrumented to obtain neuromuscular and biomechanical data on their dominant limb during the initial landing phase of a 45-cm drop jump. Multiple linear regressions determined the extent to which the three joint laxity variables combined to predict hip, knee, and ankle work absorption and stiffness. Associations between joint laxity and joint kinematics, joint kinetics, and muscle activation amplitudes were also investigated to further interpret significant relationships.
Higher AKL and GJL and lower GR combined to predict greater knee work absorption (R2 = 0.210, P = 0.002) and stiffness (R2 = 0.127, P = 0.033) and lower ankle stiffness (R2 = 0.115, P = 0.048) in females. These associations were modulated through greater peak knee extensor moments and flexion angles, lower hamstring activation, and lower ankle extensor moments. In males, joint laxity had little impact on knee energetics, but a significant association was observed between greater GJL and decreased ankle stiffness (R2 = 0.209, P = 0.012), a product of both greater peak ankle flexion and decreased ankle extensor moment.
Females with greater AKL and GJL and lower GR demonstrated a landing strategy that increased work absorption and stiffness about the knee, whereas females with greater GR demonstrated a landing style that reduced knee work absorption and stiffness. The findings suggest that AKL, GR, and GJL may represent distinct risk factors and support the need to consider more comprehensive laxity profiles as they relate to knee joint function and anterior cruciate ligament injury risk.
JOINT WORK ABSORPTION; JOINT STIFFNESS; KNEE BIOMECHANICS; SEX DIFFERENCES; ACL INJURY RISK FACTORS
In order to identify regulatory genes, we determined the heritability of gene transcripts, performed linkage analysis to identify quantitative trait loci (QTLs), and evaluated the evidence for shared genetic effects among transcripts with co-localized QTLs in non-diseased participants from 14 CEPH (Centre d'Etude du Polymorphisme Humain) Utah families. Seventy-six percent of transcripts had a significant heritability and 54% of them had LOD score ≥ 1.8. Bivariate genetic analysis of 15 transcripts that had co-localized QTLs on 4q28.2-q31.1 identified significant genetic correlation among some transcripts although no improvement in the magnitude of LOD scores in this region was noted. Similar results were found in analysis of 12 transcripts, that had co-localized QTLs in the 13q34 region. Principal-component analyses did not improve the ability to identify chromosomal regions of co-localized gene expressions.
The important role of polygenic acetabular configuration and monogenic joint laxity has again been proved in the aetiology of congenital dislocation of the hip. According to the findings reported these two genetic predispositions seem to be unrelated. The time of diagnosis in accetabular dysplasia type and joint laxity type did not differ, thus the neonatal and late-diagnosed cases do not seem to be two clear-cut entities.