L’examen clinique et les radiographies standard des membres inférieurs et des pieds comportent des biais liés à la reproductibilité et à la projection en 2 dimensions d’unobjet en 3D. La reconstruction en 3D des segments anatomiques à partir d’images biplanes acquises en position debout doit permettre de s’affranchir de ces biais, au prixd’une irradiation modérée. La 1ère partie de ce travail a posé la question de l’utilisationen pratique clinique courante des reconstructions en 3D issues de ce système, et a permis de valider la reproductibilité de celles ci ainsi que de donner des valeurs de référence de ces paramètres mesurés en 3D. La 2ème partie a consisté en l’adaptationd’un modèle de reconstruction de pieds de l’adulte à ceux de l’enfant, a permis devérifier la reproductibilité des données obtenues, ainsi que de rapporter des valeurs préliminaires de paramètres de mesures radiologiques. Enfin, la 3ème partie a étudié l’analyse complète de pieds pathologiques (pied bot varus équin) associant l’examenclinique, la morphologie radiologique (obtenues par EOS®) et la fonction du pied lors d’une analyse de la marche. Nous en concluons que si cette analyse combinée paraîtcapitale, des difficultés persistent, en particulier dans le choix du modèle pour l’analyse de la marche, les modèles les plus complets actuels étant grévés d’une incertitude liée au placement des marqueurs trop importante. / Clinical examination and standard X-rays of the lower limbs and feet have biases related to reproducibility and to 2-dimensional projection of a 3D object. The 3Dreconstruction of the anatomical segments from biplanar images acquired in a standingposition should make possible to get rid of these biases, at the cost of moderate irradiation. The 1st part of this work asked the question of the use in current clinical practice of the reconstructions in 3D resulting from this system, and allowed validationof the reproducibility of these while giving reference values of the measured parameters in 3D. The 2nd part consisted in the adaptation of a model of reconstruction of the feet of the adult to those of the child, and aimed to check the reproducibility of the data obtained, and to report preliminary values of parameters of measurements. Finally, the 3rd part studied the feasibility of a complete analysis of pathological foot (congenital clubfoot) combining clinical examination, radiological morphology (EOS® images) andfoot function with gait analysis. We conclude that while this combined analysis appears to be critical, difficulties remain, particularly in the choice of the model for walkinganalysis, with the current full-scale models being overwhelmed by uncertainty related tothe placement of markers.

A maioria dos casos de pé torto congênito tratados pelo método de Ponseti requer a secção do tendão calcâneo para correção do equino residual. Evidências clínicas sugerem que há completa cicatrização entre os cotos tendíneos, mas este processo reparativo ainda não foi suficientemente estudado. Esta investigação teve como objetivo avaliar o processo de reparação que ocorre após a secção percutânea do tendão calcâneo para a correção do equino residual no pé torto congênito idiopático tratado pelo método de Ponseti. Por meio de estudo prospectivo, foram analisadas 37 tenotomias em 26 pacientes com pé torto congênito idiopático tratados pelo método de Ponseti, com seguimento mínimo de um ano após a secção. A tenotomia foi realizada percutaneamente com agulha biselada de grosso calibre, sob sedação e anestesia local. O exame ultrassonográfico foi feito logo após a secção tendínea para assegurar que ela tenha sido completa e mensurar o afastamento entre os cotos. A reparação foi estudada por meio da ultrassonografia realizada três semanas, seis meses e um ano após a tenotomia. A ultrassonografia, realizada imediatamente após o procedimento, mostrou que, em alguns casos, feixes tendíneos residuais persistiam entre os cotos, mas foram completamente seccionados, em seguida, sob controle ultrassonográfico. Houve afastamento médio de 5,65 mm ± 2,26 (2,3 a 11,0 mm) entre os cotos tendíneos logo após a secção. Em um caso ocorreu sangramento maior que o habitual, que foi controlado com pressão local e não provocou interferência no tratamento. Após três semanas, a ultrassonografia mostrou regeneração tendínea com preenchimento do espaçamento entre os cotos por tecido hipoecoico com ecotextura irregular e com restituição da continuidade entre os cotos demonstrada dinamicamente pela transmissão de movimentos do músculo tríceps sural para o calcanhar. Seis meses após a tenotomia, o exame ultrassonográfico evidenciou que o tecido de reparação apresentava ecotextura de aspecto fibrilar e, quando comparado ao tendão normal, havia leve ou moderada hipoecogenicidade e espessamento cicatricial. Um ano após a tenotomia, o exame ultrassonográfico mostrou estrutura fibrilar na região de reparação, com ecogenicidade semelhante ao tendão normal, mas ainda apresentando espessamento tendíneo cicatricial. Em termos gerais, ocorreu rápida cicatrização após a secção percutânea do tendão calcâneo, que restabeleceu a continuidade entre os cotos. Ao final do período de observação, o tecido de reparação tendínea apresentou aspecto ultrassonográfico semelhante ao lado normal, exceto por leve espessamento, o que sugere um mecanismo de reparação predominantemente intrínseco. / Most cases of congenital clubfoot treated by the Ponseti technique require percutaneous Achilles tenotomy in order to correct the residual equinus. Clinical evidences suggest that complete healing occurs between the cut tendon stumps, but there have not yet been any detailed studies investigating this reparative process. This study was performed to assess the Achilles tendon repair after percutaneous sectioning to correct the residual equinus of clubfoot treated by the Ponseti method. A prospective study analyzed 37 tenotomies in 26 patients with clubfoot treated by the Ponseti technique, with a minimum follow-up of one year after the section. The tenotomy was performed percutaneously with a large-bore needle bevel with patient sedation and local anesthesia. Ultrasonographic scanning was performed after section to ascertain that the tenotomy had been completed and to measure the stump separation. In the follow-up period, the reparative process was followed ultrasonographically at three weeks, six months and one year post-tenotomy. The ultrasonography performed immediately after the procedure showed that in some cases, residual strands between the tendon ends persisted, and these were completely sectioned under ultrasound control. A mean retraction of 5.65 mm ± 2.26 (range, 2.3 to 11.0 mm) between tendon stumps after section was observed. Unusual bleeding occurred in one case and was controlled by digital pressure, with no interference with the final treatment. After three weeks, ultrasonography showed tendon repair with the tendon gap filled with irregular hypoechoic tissue, and also with transmission of muscle motion to the heel. Six months after tenotomy, there was structural filling with a fibrillar aspect, mild or moderate hypoechogenicity, and tendon scar thickening when compared to a normal tendon. One year after tenotomy, ultrasound showed a fibrillar structure and the echogenicity at the repair site that was similar to a normal tendon, but with persistent mild tendon scarring thickness. It was observed that there was a fast reparative process after Achilles tendon percutaneous sectioning that reestablished continuity between stumps. The reparative tissue evolved to tendon tissue with a normal ultrasonographic appearance except for mild thickening, suggesting a predominantly intrinsic repair mechanism

Clubfoot is a congenital foot disorder that, left untreated, can limit a person's mobility by making it difficult and painful to walk. Although inexpensive and reliable treatment exists, clubfoot often goes untreated in the developing world, where 80% of cases occur. Many nonprofit and non-governmental organizations are partnering with hospitals and clinics in the developing world to provide treatment for patients with clubfoot, and to train medical personnel in the use of these treatment methods. As a component of these partnerships, clinics and hospitals are collecting patient records. Some of this patient information, such as photographs, requires expert quality assessment. Such assessment may occur at a later date by a staff member in the hospital, or it may occur in a completely different location through the web interface. Photographs capture the state of a patient at a specific point in time. If a photograph is not taken correctly, and as a result, has no clinical utility, the photograph cannot be recreated because that moment in time has passed. These observations have motivated the desire to perform real-time classification of clubfoot images as they are being captured in a possibly remote and challenging environment. In the short term, successful classification could provide immediate feedback to those taking patient photos, helping to ensure that the image is of good quality and the foot is oriented correctly at the time of image capture. In the long term, this classification could be the basis for automated image analysis that could reduce the workload of a busy staff, and enable broader provision of treatment.

In recent years, microarray technology has revealed the widespread presence of submicroscopic deletions and duplications throughout the human genome termed copy number variants (CNVs). CNVs have a profound effect on gene expression and are an important source of normal genetic variation. In addition, a small proportion of CNVs contribute to genetically simple and complex disease. This thesis focuses on the identification of pathogenic CNVs contributing to the etiology of diseases with "missing heritability" using a well-planned study design individually tailored to each disease cohort to optimize CNV detection and interpretation. We performed a genome-wide analysis for CNVs in five disease cohorts with genetic etiology: autism, age-related macular degeneration (AMD), glaucoma, clubfoot, and Bardet-Biedl syndrome (BBS). Our results indicate that CNVs likely account for a proportion of cases for each disease cohort reported in this thesis. Approximately 20% of our cohort of individuals with autism from trio pedigrees harbors a CNV known to confer risk to develop autism and we identified other novel and rare variants that may play a role in autism pathogenesis. We also characterized a duplication of 2p25.3 identified in two male half-siblings with autism and determined that their mother was somatic mosaic for the duplication. Our work provides evidence that this novel CNV disrupting the genes PXDN and MYT1L are the autism-causing mutation in this pedigree. A comparative cases experimental design was used in the study of AMD and glaucoma. While no common "risk CNVs" were identified for either eye disorder, we did identify several rare overlapping CNVs disrupting genes known to play a role in the eye that may confer risk to disease in a small proportion of individuals. In a fourth genetically complex disease, clubfoot, we identified a duplication of 17q23.2 disrupting the genes TBX4, NACA2, and BRIP1 that segregates with the autosomal dominant clubfoot phenotype in a large pedigree with 16 affected individuals. In addition, the duplication is within the linkage interval identified for this family. We also applied microarray technology to analyze the genomes of individuals with BBS, an autosomal recessive disorder, for the presence of CNVs in known BBS genes as well as CNVs that elucidate novel candidate genes for BBS. From 34 BBS patients with an unidentified mutation, we observed one CNV, a heterozygous deletion of BBS10, unmasking a BBS10 frameshift mutation. A promising BBS candidate gene also emerged from our studies, implicated by an intragenic deletion of the gene MARK3 predicted to result in a frameshift and premature truncation of the protein. Functional studies utilizing antisense morpholino gene knockdown in the zebrafish provide additional evidence that MARK3 is a BBS gene as knockdown of zebrafish mark3 results in a Kupffer's Vesicle defect and a melanosome transport delay, two cardinal BBS phenotypes in the zebrafish. In addition to identifying CNVs involved in disease, the work outlined in this thesis provides valuable insight into the study design and interpretation of a genome-wide analysis of CNV. This includes the appropriate use of controls and publicly available control databases, methods for enriching for CNVs in a patient cohort to maximize efficiency and discovery, and the importance of analyzing all patient cohorts with heritable disease for the presence of CNVs disrupting known disease genes and CNVs that implicate novel genetic candidates. As the reliability and resolution of CNV detection continue to improve, allowing detection of > 1,000 CNVs in each individual genome, it becomes more important than ever to have a well-defined study design for both the detection and interpretation of CNVs.

A maioria dos casos de pé torto congênito tratados pelo método de Ponseti requer a secção do tendão calcâneo para correção do equino residual. Evidências clínicas sugerem que há completa cicatrização entre os cotos tendíneos, mas este processo reparativo ainda não foi suficientemente estudado. Esta investigação teve como objetivo avaliar o processo de reparação que ocorre após a secção percutânea do tendão calcâneo para a correção do equino residual no pé torto congênito idiopático tratado pelo método de Ponseti. Por meio de estudo prospectivo, foram analisadas 37 tenotomias em 26 pacientes com pé torto congênito idiopático tratados pelo método de Ponseti, com seguimento mínimo de um ano após a secção. A tenotomia foi realizada percutaneamente com agulha biselada de grosso calibre, sob sedação e anestesia local. O exame ultrassonográfico foi feito logo após a secção tendínea para assegurar que ela tenha sido completa e mensurar o afastamento entre os cotos. A reparação foi estudada por meio da ultrassonografia realizada três semanas, seis meses e um ano após a tenotomia. A ultrassonografia, realizada imediatamente após o procedimento, mostrou que, em alguns casos, feixes tendíneos residuais persistiam entre os cotos, mas foram completamente seccionados, em seguida, sob controle ultrassonográfico. Houve afastamento médio de 5,65 mm ± 2,26 (2,3 a 11,0 mm) entre os cotos tendíneos logo após a secção. Em um caso ocorreu sangramento maior que o habitual, que foi controlado com pressão local e não provocou interferência no tratamento. Após três semanas, a ultrassonografia mostrou regeneração tendínea com preenchimento do espaçamento entre os cotos por tecido hipoecoico com ecotextura irregular e com restituição da continuidade entre os cotos demonstrada dinamicamente pela transmissão de movimentos do músculo tríceps sural para o calcanhar. Seis meses após a tenotomia, o exame ultrassonográfico evidenciou que o tecido de reparação apresentava ecotextura de aspecto fibrilar e, quando comparado ao tendão normal, havia leve ou moderada hipoecogenicidade e espessamento cicatricial. Um ano após a tenotomia, o exame ultrassonográfico mostrou estrutura fibrilar na região de reparação, com ecogenicidade semelhante ao tendão normal, mas ainda apresentando espessamento tendíneo cicatricial. Em termos gerais, ocorreu rápida cicatrização após a secção percutânea do tendão calcâneo, que restabeleceu a continuidade entre os cotos. Ao final do período de observação, o tecido de reparação tendínea apresentou aspecto ultrassonográfico semelhante ao lado normal, exceto por leve espessamento, o que sugere um mecanismo de reparação predominantemente intrínseco. / Most cases of congenital clubfoot treated by the Ponseti technique require percutaneous Achilles tenotomy in order to correct the residual equinus. Clinical evidences suggest that complete healing occurs between the cut tendon stumps, but there have not yet been any detailed studies investigating this reparative process. This study was performed to assess the Achilles tendon repair after percutaneous sectioning to correct the residual equinus of clubfoot treated by the Ponseti method. A prospective study analyzed 37 tenotomies in 26 patients with clubfoot treated by the Ponseti technique, with a minimum follow-up of one year after the section. The tenotomy was performed percutaneously with a large-bore needle bevel with patient sedation and local anesthesia. Ultrasonographic scanning was performed after section to ascertain that the tenotomy had been completed and to measure the stump separation. In the follow-up period, the reparative process was followed ultrasonographically at three weeks, six months and one year post-tenotomy. The ultrasonography performed immediately after the procedure showed that in some cases, residual strands between the tendon ends persisted, and these were completely sectioned under ultrasound control. A mean retraction of 5.65 mm ± 2.26 (range, 2.3 to 11.0 mm) between tendon stumps after section was observed. Unusual bleeding occurred in one case and was controlled by digital pressure, with no interference with the final treatment. After three weeks, ultrasonography showed tendon repair with the tendon gap filled with irregular hypoechoic tissue, and also with transmission of muscle motion to the heel. Six months after tenotomy, there was structural filling with a fibrillar aspect, mild or moderate hypoechogenicity, and tendon scar thickening when compared to a normal tendon. One year after tenotomy, ultrasound showed a fibrillar structure and the echogenicity at the repair site that was similar to a normal tendon, but with persistent mild tendon scarring thickness. It was observed that there was a fast reparative process after Achilles tendon percutaneous sectioning that reestablished continuity between stumps. The reparative tissue evolved to tendon tissue with a normal ultrasonographic appearance except for mild thickening, suggesting a predominantly intrinsic repair mechanism

Idiopathic congenital clubfoot can be treated either operatively (comprehensive surgical release (CSR)) or conservatively (ponseti technique (PCT)). This thesis compared the mid-term outcomes after CSR and PCT treatments to a typically developing sample. A Dynamical Systems Analysis (DSA) approach and a multi-segment foot model were used to examine group differences in multi-segment foot and lower extremity kinematics, kinetics, coordination and coordination variability during walking. Ten children with clubfoot treated with PCT and seven children with clubfoot treated with CSR were evaluated retrospectively and compared to ten typically developing children. Multi-segment foot and lower extremity kinematic (240 Hz) and kinetic (1080 Hz) data were collected while participants walked barefoot at a fixed walking velocity (1.0 m/s-1 ±5%). Sagittal plane metatarsophalangeal (MTP) and three-dimensional (3D) forefoot-rearfoot, ankle, knee and hip joint range of motion (ROM) during stance and 3D ankle, knee and hip peak joint moments during push-off were calculated. A modified vector coding technique was used to quantify the multi-segment foot and lower extremity coordination and coordination variability throughout stance for forefoot-rearfoot inversion/eversion (Ff-Rf), rearfoot inversion/eversion–tibial internal/external rotation (Rf-Tib) and femur-tibia internal/external rotation (Fem-Tib) couples. Reduced MTP and forefoot-rearfoot ROM was observed in the CSR group while the PCT group demonstrated values comparable to CTR. Sagittal plane ankle ROM was similar between groups however, the CSR group demonstrated reduced frontal plane ROM compared to PCT. Peak ankle plantar flexion moment was reduced in the last 50% of stance in the clubfoot groups. The CSR group demonstrated greater knee and hip moments compared to CTR and PCT. The PCT group demonstrated lessor peak ankle eversion, knee external rotation and knee valgus moments compared to CTR. No significant differences were observed in Ff-Rf, Rf-Tib and Fem-Tib coordination and coordination variability throughout stance between the groups. PCT and CSR gait was characterized by restricted multi-segment foot motion and abnormal lower extremity joint moments; suggesting mild residual deformity. Despite residual deformity, the coordination and coordination variability results indicate that the PCT and CSR groups are not functionally limited and demonstrate similar multi-segment foot and lower extremity movement patterns as CTR.

Aim: The aim with this study is to compare different orthotic solutions for pediatric patients with congenital talipes equnivarus.  Method: A search in the databases MEDLINE, CINAHL, PubMed and Scopus were made, and studies was included after the predefined criteria. The included studies were reviewed for risk of bias and validity, relevant data was extract and analyzed with regards to the research question.  Result: The result was presented on 15 different orthotic interventions in 21 different articles. The reported outcome measures were compliance, recurrence of deformity, Pirani- and Dimeglio score, range of motion and functional outcomes.  Conclusion: Based on the results a recommendation cannot be made on what orthosis that gives the best result. Future research should focus on developing and designing an orthosis that satisfies the patient's needs. / Syfte: Syftet med detta arbete är att undersöka olika ortos-lösningar med dess inkluderade resultat för patienter med kongenital idiopatisk klumpfot. Metod: En systematisk sökning i databaserna MEDLINE, CINAHL, PubMed and Scopus genomfördes och väsentliga studier inkluderades utefter de förbestämda kriterierna. Inkluderade studiers validitet och möjliga partiskhet bedömdes samt att relevant data utifrån frågeställningen analyserades och besvarades.  Resultat: Resultatet presenterade 15 olika typer av ortoser, i 21 olika artiklar. De presenterade utfallsmåtten var inom komplians, återfall av deformationen, Pirani- och Dimeglio poäng, rörelseomfång samt inom funktionellt resultat. Slutsats: Baserat på resultat går det inte att presentera en övervägande slutsats om vilken ortos-lösning som ger bäst resultat. Framtida forskning måste utveckla och framställa ortoser som tillfredsställer och möter patienternas behov.

No / This paper provides the results of re-evaluation of a young adult individual from the Romano-British cemetery of 76 Kingsholm, Gloucester with club foot defomity by (Roberts et al 2004). Our reanalysis revealed an extensive bilateral asymmetry involving the lower and upper limb, spine and cranium and a right scoliosis, indicating more than the lower limb was affected. Consideration of the position and shape of the articulated club foot indicated a positional rather than a developmental condition, probably due to unilateral paralysis. Differential diagnosis considered congenital and acquired neuromuscular conditions; we argue that poliomyelitis is the most likely cause. Poliomyelitis is secondary to the infection with poliovirus that can affect the motor neurons from the spinal cord, causing a flaccid paralysis without sensory affection. Because the virus affects individual nerves, the paralysis is muscle-specific causing muscle imbalances and poor posture which can result in deformities and muscle disuse atrophy. Shortening of the leg is the most characteristic sign, however other typical deformations are in the lower limbs are external rotation of the knee, knee hyperestension, ankle and foot deformities (all observed in K131). The evaluation of K131’s entheses and bone structure suggests that, in life, this individual showed physical deformities consisting of a possibly visible atrophy of the left arm and leg, asymmetric gait, clubfoot and slight scoliosis which would have affected not only his appearance but also his ability to move and perform certain tasks. K131’s burial treatment is entirely normative for the period and the wider cemetery context. This could suggest that despite their impairment, this individual was not necessarily marginalised within their social context. However, historical sources account for extensive marginalisation and cruel treatment of the disabled and deformed in this period. So, whilst K131 was buried in a normative manner, it is difficult to reach definitive conclusions regarding how this individual was treated by their contemporaries.

Background: Talipes equinovarus, also termed club foot, is a congenital deformity of the ankle joint. Despite its prevalence of approximately 1 per 1000 live births, fetal talipes is relatively poorly studied since the introduction of percutaneous tendo Achilles tenotomies. Objectives: To document the associations, outcomes and prognosis of patients with antenatally diagnosed fetal talipes. The study aims to examine the association between, and prevalence of, fetal talipes and other abnormalities, structural and chromosomal, as well as the outcome in relation to postnatal surgery. The accuracy of prenatal ultrasound in diagnosing fetal talipes is also examined. Methods: A retrospective observational study was made of all cases presenting to the Fetal Medicine Unit between 1 January 2009 and 31 December 2014. All the identified cases were analysed to identify isolated talipes, associated abnormalities, and chromosomal abnormalities. The pregnancy outcomes were determined using the Astraia database as well as maternity records. When the outcome resulted in a live infant, these infants were followed up using the files at the referral hospital to determine the treatment method used and the number requiring surgery. Results: There were 155 cases, all referred to the Fetal Medicine Unit. Antenatal data included 75 who had other structural abnormalities and 75 who had isolated talipes. In five of the cases were no sufficient data could be found. Twenty-five cases were lost to follow-up, and 12 cases had no clubfoot at birth. Only one was labelled as having positional clubfoot. There were 91 live births. Of the cases of talipes with associated abnormalities, 21.19% were live births (excluding ENND). All terminations of pregnancy as well as 90.9% of intrauterine fetal deaths were complex talipes, and 94.52% of the cases of isolated talipes were live births. The most common associated abnormalities were of the central nervous system. Seventeen of the live births were lost to follow-up. Of the cases of isolated talipes, 53.19% had tenotomies and Ponseti treatment. The false positive rate of detecting fetal talipes on ultrasound was 7.74%. Conclusion: The study made it evident that complex talipes is associated with a poor pregnancy outcome defined as pregnancy loss, where isolated talipes is usually associated with a good pregnancy outcome. Ultrasound is a good diagnostic tool when diagnosing talipes antenatally but cannot diagnose the severity of the clubfoot. False negatives were not studied. The introduction of tenotomy can make a difference in the outcome of clubfoot in comparison with previous studies where tenotomies were not performed. Medical professionals need to address the importance of counselling, and a multidisciplinary team should be involved in cases involving prenatal counselling.

Aim: Through this review we aim to investigate if there is an alternative orthotic treatment for paediatric patients with idiopathic congenital talipes equinovarus showing the same maintenance of correction as the benchmark treatment but with higher adherence. Methods: A literature search was performed in the data bases MEDLINE, CINAHL and Scopus. Predetermined eligibility criteria were used to include and exclude articles. Critical appraisal was performed for the included articles. Relevant data was extracted, analyzed and presented to aid in answering the research question. Results: Of the 204 articles found in databases, seven were included in the final review. Adherence rate and relapse rate was extracted from the seven orthotic interventions. Most of the orthoses presented both better adherence and maintenance of correction than the benchmark treatment. The majority were case series, not including a comparison group and with short-term follow-up. Conclusion: The results indicate that there are orthotic designs that may be preferred over the traditional Denis Browne bar. However, the lack of high-quality evidence and standardization to detect and define a relapse and measure adherence makes it difficult to recommend an alternative orthosis with the present evidence. Factors other than the orthotic design also influence the adherence.