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Genes Jul 2022In this Special Issue of entitled "Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis", evidence is presented which suggests...
In this Special Issue of entitled "Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis", evidence is presented which suggests that congenital, idiopathic scoliosis, and arthrogryposis share similar overlapping, but also distinct etiopathogenic mechanisms, including connective tissue and neuromuscular mechanisms [...].
Topics: Arthrogryposis; Humans; Scoliosis; Skeleton
PubMed: 35885977
DOI: 10.3390/genes13071194 -
BMJ Open Oct 2022Arthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures....
INTRODUCTION
Arthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC.
METHODS AND ANALYSIS
Participants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted.
ETHICS AND DISSEMINATION
Ethical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC.
Topics: Humans; Arthrogryposis; Cross-Sectional Studies; Retrospective Studies; Registries; Genomics
PubMed: 36307157
DOI: 10.1136/bmjopen-2021-060591 -
Health and Quality of Life Outcomes Nov 2021Arthrogryposis multiplex congenita (AMC) is a group of congenital conditions characterized by joint contractures in two or more body areas. Management of AMC starts... (Review)
Review
BACKGROUND
Arthrogryposis multiplex congenita (AMC) is a group of congenital conditions characterized by joint contractures in two or more body areas. Management of AMC starts early in life and focuses on improving mobility and function through intensive rehabilitation and surgical interventions. Psychosocial wellbeing is an important determinant of health and the psychosocial experience of individuals with AMC should be considered in the management of this condition. The aim of this scoping review was to explore what is known about the psychosocial wellbeing of children and adults with AMC, to identify the outcome measures used and to explore the factors associated with psychosocial outcomes in this population.
METHODS
A comprehensive search in four databases was conducted. Articles discussing psychosocial outcomes and outcome measures used with children or adults with AMC were included. Data on the measures used, psychosocial outcomes, and factors associated with psychosocial outcomes, were extracted and analyzed descriptively and synthesized narratively.
RESULTS
Seventeen articles were included in this scoping review, ten including the pediatric population, six including adults and one article including both children and adults with AMC. The most commonly used outcome measures were the PODCI in the pediatric studies, and the SF-36 in studies on adults. In the pediatric studies, psychosocial outcomes were often secondary, compared to the studies on adults. Results showed that in both children and adults, psychosocial outcomes are comparable with the levels of the general population. Qualitative studies reflected the affective needs of this population and issues with emotional wellbeing. Factors such as fatigue and pain were associated with poorer psychosocial outcomes in adults with an impact on social relationships, intimacy and family planning.
CONCLUSION
Validated outcome measures, qualitative approaches and longitudinal studies are needed to better understand the psychosocial outcomes in AMC over time. Psychosocial support should be part of the multidisciplinary management of AMC throughout the lifespan.
Topics: Adult; Arthrogryposis; Child; Databases, Factual; Humans; Quality of Life
PubMed: 34844631
DOI: 10.1186/s12955-021-01896-5 -
Ugeskrift For Laeger Aug 2015Arthrogryposis multiplex congenita (AMC) is a sign rather than a diagnosis. It implies contractures in multiple body areas and occurs in 1:3,000-5,000 live births.... (Review)
Review
Arthrogryposis multiplex congenita (AMC) is a sign rather than a diagnosis. It implies contractures in multiple body areas and occurs in 1:3,000-5,000 live births. Primary aetiologies include neuropathic, myopathic, metabolic, end plate and vascular disorder affecting the developing foetus, including limitation of foetal space. Amyoplasia is the most common type of AMC after central nervous system disorders. Knowledge about the classification of AMC is essential to make a correct diagnosis and treatment plans. We recommend follow-up by experienced paediatric orthopaedic surgeons and neurologists.
Topics: Arthrogryposis; Humans; Infant; Syndrome
PubMed: 26320355
DOI: No ID Found -
Brain : a Journal of Neurology Oct 2023In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex...
In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.
Topics: Pregnancy; Female; Adult; Humans; Immunoglobulins, Intravenous; Receptors, Cholinergic; Myasthenia Gravis; Autoantibodies; Neuromuscular Diseases; Arthrogryposis
PubMed: 37186601
DOI: 10.1093/brain/awad153 -
The American Journal of Occupational... 2021Children with arthrogryposis multiplex congenita are often delayed in their development of reaching and object exploration, which can place them at risk for associated...
IMPORTANCE
Children with arthrogryposis multiplex congenita are often delayed in their development of reaching and object exploration, which can place them at risk for associated delays in motor and cognitive development.
OBJECTIVE
To evaluate the longitudinal assistive and rehabilitative effects of the Playskin Lift™ (hereinafter Playskin), a novel exoskeletal garment, on reaching and object exploration abilities in children with arthrogryposis.
DESIGN
Single-case ABA design with a 1-mo baseline, 4-mo intervention, and 1-mo postintervention.
SETTING
Home environment.
PARTICIPANTS
Seventeen children with arthrogryposis (ages 6-35 mo at first visit; 5 boys).
INTERVENTION
Participants used the Playskin daily for 30 to 45 min while participating in structured intervention activities to encourage reaching for objects across play spaces larger than they were typically able to.
OUTCOMES AND MEASURES
Participants were tested biweekly throughout the study with and without the Playskin using a systematic reaching assessment. Coding of reaching and object exploration behavior was performed using OpenSHAPA software; statistical analyses were conducted using Hierarchical Linear and Nonlinear Modeling software. Feasibility of the Playskin for daily home intervention was evaluated with a parent perception questionnaire.
RESULTS
Positive assistive effects (improved performance when wearing the Playskin within sessions) and rehabilitative effects (improved independent performance after the Playskin intervention) were observed with increased active range of motion, expanded reaching space, improved grasping with the ventral side of the open hand, and greater complexity and multimodality and intensity of object exploration.
CONCLUSIONS AND RELEVANCE
The Playskin may be a feasible, effective assistive and rehabilitative device to advance object interaction and learning in young children with arthrogryposis.
WHAT THIS ARTICLE ADDS
The novel exoskeletal Playskin garment improves reaching and object exploration in young children with arthrogryposis.
Topics: Adolescent; Adult; Arthrogryposis; Child; Child, Preschool; Clothing; Exploratory Behavior; Hand; Hand Strength; Humans; Male; Young Adult
PubMed: 33399059
DOI: 10.5014/ajot.2020.040972 -
Molecular Syndromology Jul 2016Arthrogryposis by definition has multiple congenital contractures. All types of arthrogryposis have decreased in utero fetal movement. Because so many things are... (Review)
Review
Arthrogryposis by definition has multiple congenital contractures. All types of arthrogryposis have decreased in utero fetal movement. Because so many things are involved in normal fetal movement, there are many causes and processes that can go awry. In this era of molecular genetics, we have tried to place the known mutated genes seen in genetic forms of arthrogryposis into biological processes or cellular functions as defined by gene ontology. We hope this leads to better identification of all interacting pathways and processes involved in the development of fetal movement in order to improve diagnosis of the genetic forms of arthrogryposis, to lead to the development of molecular therapies, and to help better define the natural history of various types of arthrogryposis.
PubMed: 27587986
DOI: 10.1159/000446617 -
Journal of Children's Orthopaedics Dec 2015Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition defined as multiple congenital joint contractures in two or more body areas. The common...
Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition defined as multiple congenital joint contractures in two or more body areas. The common pathogenesis is impaired fetal movements. Amyoplasia, the most frequent form, is a sporadically occurring condition with hypoplastic muscles and joint contractures. Distal arthrogryposis (DA) syndromes are often hereditary, and joint involvement is predominantly in the hands and feet. In a Swedish study, 131 patients with arthrogryposis were investigated. The most frequent diagnoses were amyoplasia and DA. In amyoplasia, muscle strength was found to be more important than joint range of motion (ROM) for motor function. In DA, muscle weakness was present in 44 % of investigated patients. The clinical findings were found to be highly variable between families and also within families with DA. Fetal myopathy due to sarcomeric protein dysfunction can cause DA. An early multidisciplinary team evaluation of the child with arthrogryposis for specific diagnosis and planning of treatment is recommended. Attention should be directed at the development of muscle strength with early stimulation of active movements. Immobilization should be minimized.
PubMed: 26537820
DOI: 10.1007/s11832-015-0689-1 -
Genes Dec 2021The term "arthrogryposis" is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an...
The term "arthrogryposis" is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys-Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.
Topics: Abnormalities, Multiple; Adolescent; Adult; Arthrogryposis; Child; Child, Preschool; Conjunctiva; Female; Genotype; Humans; Loeys-Dietz Syndrome; Male; Malignant Hyperthermia; Middle Aged; Mutation; Pedigree; Phenotype; Pregnancy; Pterygium; Skin Abnormalities
PubMed: 35052370
DOI: 10.3390/genes13010029 -
Frontiers in Physiology 2020Distal arthrogryposis (DA) is a skeletal muscle disorder which can be classified under a broader term as Arthrogryposis multiplex contractures. DA is characterized by... (Review)
Review
Distal arthrogryposis (DA) is a skeletal muscle disorder which can be classified under a broader term as Arthrogryposis multiplex contractures. DA is characterized by the presence of joint contractures at various parts of the body, particularly in distal extremities. It is identified as an autosomal dominant and a rare X-linked recessive disorder associated with increased connective tissue formation around joints in such way that immobilizes muscle movement causing deformities. DA is again classified into various types since it manifests as a range of conditions representing different etiologies. Myopathy is one of the most commonly listed etiologies of DA. The mutations in sarcomeric protein-encoding genes lead to decreased sarcomere integrity, which is often associated with this disorder. Also, skeletal disorders are often associated with cardiac disorders. Some studies mention the presence of cardiomyopathy in patients with skeletal dysfunction. Therefore, it is hypothesized that the congenitally mutated protein that causes DA can also lead to cardiomyopathy. In this review, we will summarize the different forms of DA and their clinical features, along with gene mutations responsible for causing DA in its different forms. We will also examine reports that list mutations also known to cause heart disorders in the presence of DA.
PubMed: 32670090
DOI: 10.3389/fphys.2020.00689