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Judith G Hall - One of the best experts on this subject based on the ideXlab platform.
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deformations associated with Arthrogryposis
American Journal of Medical Genetics Part A, 2021Co-Authors: Judith G HallAbstract:Fetal movement is essential to normal human development. If the fetus does not move for whatever reason, then multiple organs and organ systems develop secondary and tertiary effects not normally present. Most of these are deformations with secondary structural damage.
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summary of the 3rd international symposium on Arthrogryposis
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Noemi Dahanoliel, Judith G Hall, Ani Samargian, Bonita Sawatzky, Harold J P Van BosseAbstract:The 1st international symposium on Arthrogryposis (ISA) was held in 2007 in Birmingham, UK, to bring together a multinational group of experts in the field of Arthrogryposis, patients and their families to discuss various aspects of care for individuals with Arthrogryposis Multiplex Congenita (AMC). These "lessons learnt" set the tone for the 2nd ISA held in Saint Petersburg, Russia in 2014. Clinical and research advances have recently been made in the field of Arthrogryposis and were shared at the 3rd ISA, in Philadelphia, in 2018. Highlights of the 3ISA and future directions are presented.
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gene ontology analysis of Arthrogryposis multiple congenital contractures
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Jeff Kiefer, Judith G HallAbstract:In 2016, we published an article applying Gene Ontology Analysis to the genes that had been reported to be associated with Arthrogryposis (multiple congenital contractures) (Hall & Kiefer, 2016). At that time, 320 genes had been reported to have mutations associated with Arthrogryposis. All were associated with decreased fetal movement. These 320 genes were analyzed by biological process and cellular component categories, and yielded 22 distinct groupings. Since that time, another 82 additional genes have been reported, now totaling 402 genes, which when mutated, are associated with Arthrogryposis (Arthrogryposis multiplex congenita). So, we decided to update the analysis in order to stimulate further research and possible treatment. Now, 29 groupings can be identified, but only 19 groups have more than one gene.
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fetal cervical hyperextension in Arthrogryposis
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Judith G HallAbstract:Perhaps the most dramatic position of a newborn after delivery is when there is hyperextension of the neck and spine. It will have been presented in utero and today, almost always, such babies will have been delivered by C-section. The associated anomalies are variable. The process(es) that can lead to cervical hyperextension is/are largely unknown. The outcome is variable from lethal to completely resolve. Individuals with Arthrogryposis and in particular with Amyoplasia appear to have an increased frequency of neck, cervical, and spine hyperextension at birth. We present here 41 cases of Arthrogryposis (mainly Amyoplasia) with fetal cervical hyperextension. The outlook is surprisingly good if spinal cord trauma does not occur. Ultrasound late in pregnancy when Arthrogryposis is recognized prenatally should determine whether cervical hyperextension has developed, so that appropriate preventive measures can be taken.
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classification of Arthrogryposis
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Judith G Hall, Eva Kimber, Klaus DieterichAbstract:There is a need for a system to classify various forms of Arthrogryposis. None is satisfactory or complete. Nevertheless, several have been developed to meet the needs of clinicians, prenatal diagnosticians, researchers, and basic scientists. They all await more insight into basic mechanisms.
Matthew B Dobbs - One of the best experts on this subject based on the ideXlab platform.
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Models of Distal Arthrogryposis and Lethal Congenital Contracture Syndrome
'MDPI AG', 2021Co-Authors: Julia Whittle, Matthew B Dobbs, Aaron Johnson, Christina A GurnettAbstract:Distal Arthrogryposis and lethal congenital contracture syndromes describe a broad group of disorders that share congenital limb contractures in common. While skeletal muscle sarcomeric genes comprise many of the first genes identified for Distal Arthrogyposis, other mechanisms of disease have been demonstrated, including key effects on peripheral nerve function. While Distal Arthrogryposis and Lethal Congenital Contracture Syndromes display superficial similarities in phenotype, the underlying mechanisms for these conditions are diverse but overlapping. In this review, we discuss the important insights gained into these human genetic diseases resulting from in vitro molecular studies and in vivo models in fruit fly, zebrafish, and mice
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mybpc1 mutations impair skeletal muscle function in zebrafish models of Arthrogryposis
Human Molecular Genetics, 2013Co-Authors: Jillian G Buchan, Matthew B Dobbs, David M Alvarado, Kevin Mccall, Anupama Vydyanath, Pradeep K Luther, Matthew I Goldsmith, Christina A GurnettAbstract:Myosin-binding protein C1 (MYBPC1) is an abundant skeletal muscle protein that is expressed predominantly in slow-twitch muscle fibers. Human MYBPC1 mutations are associated with distal Arthrogryposis type 1 and lethal congenital contracture syndrome type 4. As MYBPC1 function is incompletely understood, the mechanism by which human mutations result in contractures is unknown. Here, we demonstrate using antisense morpholino knockdown, that mybpc1 is required for embryonic motor activity and survival in a zebrafish model of Arthrogryposis. Mybpc1 morphant embryos have severe body curvature, cardiac edema, impaired motor excitation and are delayed in hatching. Myofibril organization is selectively impaired in slow skeletal muscle and sarcomere numbers are greatly reduced in mybpc1 knockdown embryos, although electron microscopy reveals normal sarcomere structure. To evaluate the effects of human distal Arthrogryposis mutations, mybpc1 mRNAs containing the corresponding human W236R and Y856H MYBPC1 mutations were injected into embryos. Dominant-negative effects of these mutations were suggested by the resultant mild bent body curvature, decreased motor activity, as well as impaired overall survival compared with overexpression of wild-type RNA. These results demonstrate a critical role for mybpc1 in slow skeletal muscle development and establish zebrafish as a tractable model of human distal Arthrogryposis.
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exome sequencing identifies an myh3 mutation in a family with distal Arthrogryposis type 1
Journal of Bone and Joint Surgery American Volume, 2011Co-Authors: David M Alvarado, Christina A Gurnett, Jillian G Buchan, Matthew B DobbsAbstract:Distal Arthrogryposis is characterized by contractures of the distal regions of the hands and feet1. The severe types of distal Arthrogryposis, types 2A (also called Freeman-Sheldon syndrome) and 2B (also called Sheldon-Hall syndrome), include facial involvement and scoliosis, whereas distal Arthrogryposis type 1 (DA1) does not2. Distal Arthrogryposis type 1 affects approximately one in 10,000 children and represents the most common type3. Multiple genes encoding proteins in the sarcomere, including myosin heavy chain 3 (MYH3), myosin heavy chain 8 (MYH8), tropomyosin 2 (TPM2), troponin I2 (TNNI2), troponin T3 (TNNT3), and myosin binding protein C1 (MYBPC1)4-9, have been implicated in distal Arthrogryposis syndromes. Although MYH3 mutations account for nearly all cases of Freeman-Sheldon syndrome (type 2A) and nearly one-third of all cases of Sheldon-Hall syndrome (type 2B), to our knowledge MYH3 mutations have not been described in patients with distal Arthrogryposis type 14. Previous studies have shown that mutations in known genes are rare causes of distal Arthrogryposis type 19,10; therefore, genetic heterogeneity is expected and additional causative genes remain to be identified. Because of the large number of genes as well as the relatively large size of the genes already implicated in distal Arthrogryposis syndromes, new methods to sequence all genes are necessary to effectively define the genetic basis of distal Arthrogryposis in individual families. Exome sequencing is a new genetic tool that uses next-generation sequencing methods to identify mutations within the coding exons of the entire human genome (the “exome”)11. Because the exome comprises just 1% of the genome, the cost of sequencing only the exons is currently only a fraction of the cost of whole-genome sequencing. The next-generation exome capture and sequencing methods that were used in this study represent a substantial advance in research methods and, despite their limitations, these methods are likely to soon have a major impact on the diagnosis of patients with inherited musculoskeletal disorders. For instance, our identification of a mutation in MYH3 in the family described in this study broadens the phenotype associated with MYH3 mutations to include distal Arthrogryposis type 1 and suggests that there may be substantial overlap between types 1, 2A, and 2B. Distal Arthrogryposis type 1 should be considered in the differential diagnosis of isolated clubfoot, particularly in the presence of even minor hand contractures in the patient or family members.
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skeletal muscle contractile gene tnnt3 myh3 tpm2 mutations not found in vertical talus or clubfoot
Clinical Orthopaedics and Related Research, 2009Co-Authors: Christina A Gurnett, Matthew B Dobbs, Farhang Alaee, David M Desruisseau, Stephanie BoehmAbstract:Arthrogryposis presents with lower limb contractures that resemble clubfoot and/or vertical talus. Recently, mutations in skeletal muscle contractile genes MYH3 (myosin heavy chain 3), TNNT3 (troponin T3), and TPM2 (tropomyosin 2) were identified in patients with distal Arthrogryposis DA2A (Freeman-Sheldon syndrome) or DA2B (Sheldon-Hall syndrome). We asked whether the contractile genes responsible for distal Arthrogryposis are also responsible for cases of familial clubfoot or vertical talus. We determined the frequency of MYH3, TNNT3, and TPM2 mutations in patients with idiopathic clubfoot, vertical talus, and distal Arthrogryposis type 1 (DA1). We resequenced the coding exons of the MYH3, TNNT3, and TPM2 genes in 31 patients (five with familial vertical talus, 20 with familial clubfoot, and six with DA1). Variants were evaluated for segregation with disease in additional family members, and the frequency of identified variants was determined in a control population. In one individual with DA1, we identified a de novo TNNT3 mutation (R63H) previously identified in an individual with DA2B. No other causative mutations were identified, though we found several previously undescribed single-nucleotide polymorphisms of unknown importance. Although mutations in MYH3, TNNT3, and TPM2 are frequently associated with distal Arthrogryposis syndromes, they were not present in patients with familial vertical talus or clubfoot. The TNNT3 R63H recurrent mutation identified in two unrelated individuals may be associated with either DA1 or DA2B.
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results of the ponseti method in patients with clubfoot associated with Arthrogryposis
The Iowa orthopaedic journal, 2008Co-Authors: Jose A Morcuende, Matthew B Dobbs, Steven L FrickAbstract:Clubfoot associated with Arthrogryposis has been traditionally considered very resistant to manipulation and casting, and therefore has required surgical correction. The purpose of this study was to evaluate the results of the Ponseti method of clubfoot casting in this patient population. We reviewed the records of patients with clubfoot associated with Arthrogryposis consecutively treated at our respective institutions from January 1992 to December 2004. All patients were treated by serial manipulations and casting following the principles of the Ponseti method. Main outcome measures included initial correction of the deformity, relapses and the need for surgical releases or any other surgeries. Average age at last follow up was 4.6 years. There were 16 patients, all with bilateral deformities (32 clubfeet). there were 11 males and 5 females. Nine patients had both upper and lower extremity involvement. Seven patients had previous treatment elsewhere and one patient had an Achilles tenotomy. Initial correction was obtained in all but 1 patient. Average number of casts required for correction was 7 (range: 5 to 12). Average post-tenotomy dorsiflexion was 5 degrees. One patient required a posterior-medial release (PMR) for insufficient initial correction. Four cases required subsequent surgery for relapses (1 bilateral PMR with a repeat left PMR; 2 posterior releases (PR), 1 PR and anterior tibialis transfer (ATT), and 1 ATT). No talectomies were required. This study demonstrates that the Ponseti method is very effective for the correction of patients with clubfoot associated to Arthrogryposis. Although this deformity is more rigid than in idiopathic clubfoot, many cases can be corrected when started in the first few weeks after birth.
Noemi Dahanoliel - One of the best experts on this subject based on the ideXlab platform.
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rehabilitation needs of youth with Arthrogryposis multiplex congenita perspectives from key stakeholders
Disability and Rehabilitation, 2020Co-Authors: Noemi Dahanoliel, Caroline Elfassy, Vasiliki Betty Darsaklis, Laurie Snider, Cynthia Gagnon, Reggie C HamdyAbstract:Background: Arthrogryposis multiplex congenita is a term used to describe congenital contractures in at least two body parts with an overall prevalence of 1 in 3000 live births. It is often caused by lack of fetal movement in utero and presents as contractures of varying severity, which may affect the upper and lower extremities, the spine and jaw. Currently, no practice recommendations exist to inform best clinical practice for Arthrogryposis multiplex congenita.Purpose: To identify the needs surrounding rehabilitation as experienced by youth with Arthrogryposis multiplex congenita, caregivers, and clinicians and to propose solutions to develop family- and client-centred rehabilitation recommendations.Materials and methods: A modified experience-based co-design methodology was used where qualitative interviews were conducted with key stakeholders.Results: Twenty-seven participants completed the interviews and demographic information was collected where early-active rehabilitation began at birth in most cases and became less frequent through adolescence. Three overarching themes were determined for each stakeholder group.Conclusions: All participants reported that early-active rehabilitation is beneficial as it helps determine future treatments. Transition times and participation need to be at the center of interventions to ensure that the needs of youth with Arthrogryposis multiplex congenita are being met. The development a condition-specific outcome-measure and rehabilitation practice recommendations will assist clinicians in addressing the needs of youth with Arthrogryposis multiplex congenita.Implications for rehabilitationArthrogryposis multiplex congenita presents in at least two different areas of the body as multiple congenital contractures of varying severity which may affect the upper and lower extremities, spine and jaw.Youth with Arthrogryposis multiplex congenita identified participation as an essential component of their life, however caregivers and clinicians did not emphasize this need.Gathering information from different stakeholders is important to ensure varying needs are addressed.Rehabilitation was reported to be beneficial from early childhood to late adolescence by youth, caregivers, and clinicians.Frequency of rehabilitation diminished over time, emphasizing the need for continued follow-up into adolescence.
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summary of the 3rd international symposium on Arthrogryposis
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Noemi Dahanoliel, Judith G Hall, Ani Samargian, Bonita Sawatzky, Harold J P Van BosseAbstract:The 1st international symposium on Arthrogryposis (ISA) was held in 2007 in Birmingham, UK, to bring together a multinational group of experts in the field of Arthrogryposis, patients and their families to discuss various aspects of care for individuals with Arthrogryposis Multiplex Congenita (AMC). These "lessons learnt" set the tone for the 2nd ISA held in Saint Petersburg, Russia in 2014. Clinical and research advances have recently been made in the field of Arthrogryposis and were shared at the 3rd ISA, in Philadelphia, in 2018. Highlights of the 3ISA and future directions are presented.
Michael J Bamshad - One of the best experts on this subject based on the ideXlab platform.
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Arthrogryposis a review and update
Journal of Bone and Joint Surgery American Volume, 2009Co-Authors: Michael J Bamshad, Ann E Van Heest, David E PleasureAbstract:Congenital contractures can be divided into two groups: isolated contractures and multiple contractures (Fig. 1). Isolated congenital contractures affect only a single area of the body; the most common isolated contracture is congenital clubfoot, which occurs in one of every 500 live births1. Fig. 1 Types of congenital contractures. The term Arthrogryposis is often used as shorthand to describe multiple congenital contractures that affect two or more different areas of the body. Arthrogryposis is not a specific diagnosis, but rather a clinical finding, and it is a characteristic of more than 300 different disorders2,3. The overall prevalence of Arthrogryposis is one in 3000 live births4. The inheritance, natural history, treatment guidelines, and outcomes of Arthrogryposis vary among disorders, underscoring the importance of making a specific diagnosis in each child1,5-10. The purpose of this article is to present the current state of knowledge about the classification, etiology, and management of children with various types of Arthrogryposis. To establish a differential diagnosis, it is important to first decide whether a child has normal neurological function. A normal neurological examination suggests that Arthrogryposis is due to amyoplasia, a distal Arthrogryposis, a generalized connective tissue disorder, or fetal crowding. In contrast, an abnormal neurological examination indicates that movement in utero was diminished as a result of an abnormality of the central or peripheral nervous system, the motor end plate, or muscle. ### Amyoplasia Amyoplasia (A = no; myo = muscle; plasia = growth) is a distinct form of Arthrogryposis with characteristic clinical features as shown in Figure 2: the shoulders are usually internally rotated and adducted, the elbows are extended, the wrists are flexed and ulnarly deviated, the fingers are stiff, and the thumbs are positioned in the palm. In the lower limbs, …
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juvenile macular dystrophy and forearm pronation supination restriction presenting with features of distal Arthrogryposis type 5
American Journal of Medical Genetics Part A, 2009Co-Authors: Marco Castori, Rosanna Rinaldi, Luana Barboni, Paolo Tanzilli, Michael J Bamshad, Paola GrammaticoAbstract:The distal arthrogryposes are a heterogeneous group of conditions characterized by congenital contractures of hands and feet, and autosomal dominant inheritance. The concurrence of ophthalmoplegia and additional ocular findings distinguish distal Arthrogryposis type 5 (DA5). This rare subtype has been described in 33 patients to date and its clinical spectrum of physical findings is still poorly understood. We report on a family with three individuals with DA5. The index case came to our attention because of restricted forearm pronation-supination and juvenile macular dystrophy. Further examination revealed short stature, firm muscles, stiff spine with lumbar hyperlordosis, generalized mild limitation of the large joints, external rotation of the hips, unilateral ptosis, exophoria, and abnormal photopic and scotopic responses on electroretinogram testing. However, there was no overt evidence of contractures of the distal joints. Examination of other affected family members revealed restricted range of movement of the small joints together with ulnar deviation of the fingers, and clarified the diagnosis. Our observations suggest that DA5 may have a very mild musculoskeletal phenotype and it should be considered in the differential of congenital contracture syndromes even in the absence of obvious distal joint involvement. Our observations also suggest that fundoscopy and ocular electrophysiological studies might be helpful in the evaluation of patients with otherwise unclassified distal arthrogryposes. Am. J. Med. Genet. © 2009 Wiley-Liss, Inc.
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mutations in embryonic myosin heavy chain myh3 cause freeman sheldon syndrome and sheldon hall syndrome
Nature Genetics, 2006Co-Authors: Reha M Toydemir, Ann Rutherford, Frank G Whitby, Lynn B Jorde, John C Carey, Michael J BamshadAbstract:The genetic basis of most conditions characterized by congenital contractures is largely unknown. Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple congenital contracture (that is, Arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal Arthrogryposis. FSS and SHS mutations affect different myosin residues, demonstrating that MYH3 genotype is predictive of phenotype. A structure-function analysis shows that nearly all of the MYH3 mutations are predicted to interfere with myosin's catalytic activity. These results add to the growing body of evidence showing that congenital contractures are a shared outcome of prenatal defects in myofiber force production. Elucidation of the genetic basis of these syndromes redefines congenital contractures as unique defects of the sarcomere and provides insights about what has heretofore been a poorly understood group of disorders.
Harold J P Van Bosse - One of the best experts on this subject based on the ideXlab platform.
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summary of the 3rd international symposium on Arthrogryposis
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2019Co-Authors: Noemi Dahanoliel, Judith G Hall, Ani Samargian, Bonita Sawatzky, Harold J P Van BosseAbstract:The 1st international symposium on Arthrogryposis (ISA) was held in 2007 in Birmingham, UK, to bring together a multinational group of experts in the field of Arthrogryposis, patients and their families to discuss various aspects of care for individuals with Arthrogryposis Multiplex Congenita (AMC). These "lessons learnt" set the tone for the 2nd ISA held in Saint Petersburg, Russia in 2014. Clinical and research advances have recently been made in the field of Arthrogryposis and were shared at the 3rd ISA, in Philadelphia, in 2018. Highlights of the 3ISA and future directions are presented.
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background to the 2nd international symposium on Arthrogryposis
Journal of Pediatric Orthopaedics, 2017Co-Authors: Ruth Lester, Judith G Hall, Eva Ponten, Harold J P Van BosseAbstract:Arthrogryposis multiplex congenital is a relatively uncommon condition, with little consensus on treatment. In 2007, the 1st International Symposium on Arthrogryposis was held in Birmingham, United Kingdom, to bring together patients, their families, and a multinational group of health care experts in the field of Arthrogryposis, to discuss various aspects of the care of patients with Arthrogryposis multiplex congenital. From that meeting, there was a coalescence of thought on diagnosis and classification, a sharing of practices on treatments and their outcomes, and an agreement on future directions. At the beginning of the 2nd International Symposium on Arthrogryposis held in Saint Petersburg in September 2014, Russia, these "lessons learnt" were synopsized to set the tone for the new meeting.
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summary of the 2nd international symposium on Arthrogryposis st petersburg russia september 17 19 2014
American Journal of Medical Genetics Part A, 2015Co-Authors: Judith G Hall, Eva Ponten, Olga Agranovich, Harold J P Van BosseAbstract:Enormous progress has been made in understanding the etiology and therapies for Arthrogryposis (multiple congenital contractures). A 2nd International Symposium on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg, Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this special meeting. Care providers from multiple disciplines from all over the world representing 18 nations attended. Participants included: Pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st symposium established the need for a collaborative and interdisciplinary approach to the treatment of Arthrogryposis, engagement of parent support organizations, and the aim for more research. The Second Symposium highlighted the continuing need for more research on various therapies, identification of different types of Arthrogryposis, standardized descriptions of severity, development of new orthotics, improved prenatal diagnosis, and studying adult outcome. Major progress has been made on both upper and lower limb treatments. © 2015 Wiley Periodicals, Inc.
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Treatment of Knee Flexion Contractures in Patients With Arthrogryposis
Journal of pediatric orthopedics, 2007Co-Authors: Harold J P Van Bosse, David S. Feldman, Jack Anavian, Debra A. SalaAbstract:Background:Knee flexion contractures in children with Arthrogryposis are difficult to treat. The purpose of this study was to assess the effectiveness of posterior knee releases and gradual contracture distraction with an Ilizarov external fixator in correcting and maintaining correction of knee fle
