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Journal of Pediatric Orthopedics Mar 2024Arthrogryposis (AMC) is a descriptive term to characterize a child born with multiple joint contractures. Treatment aims to improve functional independence, yet the... (Observational Study)
Observational Study
BACKGROUND
Arthrogryposis (AMC) is a descriptive term to characterize a child born with multiple joint contractures. Treatment aims to improve functional independence, yet the literature objectively describing functional independence in this population is scarce. This study aimed to describe the functional independence of children with AMC through the lens of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) and observational activities of daily living (ADL) tasks.
METHODS
Patients with AMC between the ages of 3 and 12 years participated in this prospective study. Parents completed the PEDI-CAT while a trained occupational therapist observed children as they completed a checklist of functional ADL tasks. Patients were grouped according to developmental age groups: "preschoolers" (3 to 5 y), "early school-age" (6 to 9 y), and "late school-age" (10 to 12 y). Patient's PEDI-CAT normative scores were described, comparing the study population to typically developing children, and differences in each domain were examined between developmental age groups. The observed ADL tasks completed were also described, and differences in scores were examined between developmental age groups.
RESULTS
Forty-four patients (mean age of 7±2.86 y) were enrolled. The distribution between age groups was nearly even. Mean daily activities T -score for patients with AMC was 25.80±11.98 and the mean mobility T -score was 17.39±9.77. Late school-age children scored significantly lower than preschool-age children in both of these domains ( P <0.01). Observed ADL tasks demonstrated a high level of required assistance for patients (range: 27.3% to 61.4%), although older school-age children did show greater independence with tested activities than preschool-age children ( P =0.05).
CONCLUSION
Children with AMC are significantly limited in functional independence, particularly regarding age-appropriate daily activities and mobility. Outcomes from this study provide a reference to help gauge the results of nonoperative and surgical treatment toward improving functional independence in this population.
LEVEL OF EVIDENCE
Level III: prognostic study.
Topics: Child, Preschool; Child; Humans; Activities of Daily Living; Disabled Children; Functional Status; Arthrogryposis; Prospective Studies; Disability Evaluation
PubMed: 38053409
DOI: 10.1097/BPO.0000000000002584 -
Journal of Pediatric Orthopedics Apr 2024Congenital dislocation of the knee (CDK) may be idiopathic or associated with another condition, such as Larsen syndrome or arthrogryposis. Surgical reduction of type-3...
BACKGROUND
Congenital dislocation of the knee (CDK) may be idiopathic or associated with another condition, such as Larsen syndrome or arthrogryposis. Surgical reduction of type-3 dislocation may require quadricepsplasty (QP) or femoral diaphyseal shortening (FS). Because it is unknown which treatment is more effective, we evaluated long-term outcomes using patient-reported questionnaires and gait analysis, comparing results by surgery type and underlying diagnosis.
METHODS
Twelve patients (mean age, 19 mo) were treated surgically for CDK from 1985 to 2015 and studied 9 to 30 years postoperatively. Three participants had idiopathic CDK, 5 had Larsen syndrome, and 4 had arthrogryposis. Eleven knees underwent QP and 7 underwent FS. Participants were evaluated in our movement science laboratory and completed patient-reported outcome questionnaires. Data were compared with healthy, age-matched control values at the same visit.
RESULTS
Surgically treated knees had less flexion during swing (P<0.01), less overall motion (P<0.01), greater coronal instability (P<0.04), and slower gait (P<0.01) compared with controls. QP knees had more instability in midstance (P=0.03) and less flexion during gait compared with FS knees, less sagittal power generation than controls (P<0.01), and trended toward lower scores on Knee Injury and Osteoarthritis Outcome and Lysholm Knee Questionnaires than FS patients did. The idiopathic group had the gait most similar to that of controls, followed by the Larsen syndrome group and then the arthrogryposis group. The idiopathic group also had a better UCLA Activity Score (P=0.03) than the arthrogryposis group did.
CONCLUSIONS
Surgical treatment of type-3 CDK will not likely restore normal knee function, suggesting teratologic joint abnormality. In this small series, FS produced better gait mechanics and patient-reported outcomes compared with QP. Not surprisingly, patients with idiopathic CDK had better outcomes than those with a syndromic diagnosis, likely related to having only a single joint affected.
LEVEL OF EVIDENCE
Level III.
PubMed: 38666580
DOI: 10.1097/BPO.0000000000002711 -
Disability and Rehabilitation Oct 2023To identify the perceived facilitators and barriers among clinicians and managers about the uptake of expert guidance for rehabilitation of children with arthrogryposis...
PURPOSE
To identify the perceived facilitators and barriers among clinicians and managers about the uptake of expert guidance for rehabilitation of children with arthrogryposis multiplex congenita (AMC) in practice.
METHODS
Qualitative study using individual interviews, guided by the Theoretical Domains Framework (TDF), to explore beliefs and to identify facilitators and barriers to guidance uptake. Interviews were conducted with a convenience sample of 15 clinicians working with children with AMC and four pediatric clinical managers using Microsoft Teams©. Interviews were then transcribed verbatim and analyzed by four independent reviewers using deductive and inductive coding.
RESULTS
The TDF domains of Environmental Context and Resources, Behavioural Regulation, Reinforcement, Beliefs about Consequences, and Social Influences were shared amongst clinicians and clinical managers across North America and Europe as being relevant and influential on the target behaviour of using rehabilitation expert guidance to manage pediatric patients. Among clinicians only, the domain Memory, Attention, and Decision-Making Processes was also found relevant. Among managers only, the domain Social/Professional Role and Identity was found relevant.
CONCLUSIONS
Coupling shared relevant domains amongst clinicians and managers with individual supports and barriers helps to map out what is needed to promote the uptake of rehabilitation guidance at multiple levels.
PubMed: 37782214
DOI: 10.1080/09638288.2023.2263361 -
Orphanet Journal of Rare Diseases Aug 2023Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly... (Review)
Review
BACKGROUND
Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome.
METHODS
We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases.
RESULTS
Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized.
CONCLUSION
This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.
Topics: Humans; East Asian People; Arthrogryposis; Asian People; Mutation
PubMed: 37644569
DOI: 10.1186/s13023-023-02874-4 -
Clinical Genetics Jun 2024Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal...
Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.
Topics: Humans; Female; Male; Arthrogryposis; Phenotype; Fetus; Exome Sequencing; Contracture; Pregnancy; Ultrasonography, Prenatal; Mutation; Abnormalities, Multiple
PubMed: 38278647
DOI: 10.1111/cge.14490 -
Cureus Sep 2023Background Congenital myasthenic syndromes (CMS) are a group of hereditary diseases of the neuromuscular junction. CMS are extremely rare diseases that cause hypotonia;...
Background Congenital myasthenic syndromes (CMS) are a group of hereditary diseases of the neuromuscular junction. CMS are extremely rare diseases that cause hypotonia; however, scoliosis may theoretically be helpful in early diagnosis of CMS. The objective of this study was to emphasize the clinical features of the patients we followed up with the diagnosis of CMS and demonstrate that scoliosis is an important finding in the diagnosis of CMS in the presence of hypotonia/weakness. Materials and methods In this retrospective study, data were retrieved by examining the digital files of the patients who presented to Aydın Maternity and Children's Hospital and Elazığ Fethi Sekin City Hospital Pediatric Neurology Clinics between 2018 and 2023. The diagnosis of CMS was strongly supported by a combination of clinical characteristics, neurophysiological studies, genetic tests, AChR antibodies, and serum creatine kinase measurement. The presence of scoliosis was evaluated by an orthopedics and traumatology specialist. Results Eleven CMS patients with accompanying scoliosis were included in the study. The mean age of the patients was 69.4±39.28 months. The age of the patients at the time of diagnosis was 42.7±35.19 months. Among the patients, eight were males (72.7%), and three were females (27.2%). Seven patients (63.6%) had COLQ mutations. Electromyography was conducted on eight patients, with one of them showing no pathological findings, while seven exhibited decremental responses. All patients had ptosis, while six (54.5%) had bulbar signs. Ten patients (90.9%) had weakness. Nine patients (81.8%) experienced frequent recurrent lower respiratory tract infections. Both the patient with CHAT mutation and RAPSN mutation had arthrogryposis. Conclusion In this study, CMS stands out as an essential consideration in the differential diagnosis, particularly when scoliosis accompanies early-onset muscle weakness.
PubMed: 37766777
DOI: 10.7759/cureus.45875 -
International Journal of Molecular... Aug 2023Congenital arthrogryposis (CA) refers to the presence of multiple contractures at birth. It is a feature of several inherited syndromes, notable amongst them are... (Review)
Review
Congenital arthrogryposis (CA) refers to the presence of multiple contractures at birth. It is a feature of several inherited syndromes, notable amongst them are disorders of collagen formation. This review aims to characterize disorders that directly or indirectly impact collagen structure and function leading to CA in search for common phenotypic or pathophysiological features, possible genotype-phenotype correlation, and potential novel treatment approaches based on a better understanding of the underlying pathomechanism. Nine genes, corresponding to five clinical phenotypes, were identified after a literature search. The most notable trend was the extreme phenotype variability. Clinical features across all syndromes ranged from subtle with minimal congenital contractures, to severe with multiple congenital contractures and extra-articular features including skin, respiratory, or other manifestations. Five of the identified genes were involved in the function of the Lysyl Hydroxylase 2 or 3 enzymes, which enable the hydroxylation and/or glycosylation of lysyl residues to allow the formation of the collagen superstructure. Whilst current treatment approaches are post-natal surgical correction, there are also potential in-utero therapies being developed. Cyclosporin A showed promise in treating collagen VI disorders although there is an associated risk of immunosuppression. The treatments that could be in the clinical trials soon are the splice correction therapies in collagen VI-related disorders.
Topics: Humans; Arthrogryposis; Syndrome; Homeostasis; Collagen; Contracture
PubMed: 37686358
DOI: 10.3390/ijms241713545 -
PLoS Neglected Tropical Diseases Nov 2023Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse...
INTRODUCTION
Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse muscle impairment, a high frequency of arthrogryposis, and microphthalmia. Cardiac impairment in CZS has rarely been evaluated. Our study assessed morphology and biventricular cardiac function in children with CZS and advanced neurological dysfunction.
METHODS
This cross-sectional study was conducted on 52 children with CZS (Zika group; ZG) and 25 healthy children (control group; CG) in Paraiba, Brazil. Clinical evaluation, electrocardiogram (EKG), and transthoracic echocardiogram (TTE) were performed on all children. Additionally, troponin I and natriuretic peptide type B (BNP) levels, the degree of cerebral palsy, and neuroimaging findings were assessed in the ZG group.
RESULTS
The median age of the study population was 5 years in both groups, and 40.4% (ZG) and 60% (CG) were female. The most prevalent electrocardiographic alteration was sinus arrhythmia in both the ZG (n = 9, 17.3%) and CG (n = 4, 16%). The morphological parameters adjusted for Z score were as follows: left ventricular (LV) end-diastolic diameter in ZG: -2.36 [-5.10, 2.63] vs. CG: -1.07 [-3.43, 0.61], p<0.001); ascending aorta (ZG: -0.09 [-2.08, 1.60] vs. CG: 0.43 [-1.47, 2.2], p = 0.021); basal diameter of the right ventricle (RV) (ZG: -2.34 [-4.90, 0.97] vs. CG: -0.96 [-2.21, 0.40], p<0.01); and pulmonary artery dimension (ZG: -2.13 [-5.99, 0.98] vs. CG: -0.24 [-2.53, 0.59], p<0.01). The ejection fractions (%) were 65.7 and 65.6 in the ZG and CG, respectively (p = 0.968). The left atrium volume indices (mL/m2) in the ZG and CG were 13.15 [6.80, 18.00] and 18.80 [5.90, 25.30] (p<0.01), respectively, and the right atrium volume indices (mL/m2) were 10.10 [4.90, 15.30] and 15.80 [4.10, 24.80] (p<0.01). The functional findings adjusted for Z score were as follows: lateral systolic excursion of the mitral annular plane (MAPSE) (ZG: 0.36 [-2.79, 4.71] vs. CG: 1.79 [-0.93, 4.5], p = 0.001); tricuspid annular plane systolic excursion (TAPSE) (ZG: -2.43 [-5.47, 5.09] vs. CG: 0.07 [-1.98, 3.64], p<0.001); and the S' of the RV (ZG: 1.20 [3.35, 2.90] vs. CG: -0.20 [-2.15, 1.50], p = 0.0121). No differences in biventricular strain measurements were observed between the groups. Troponin I and BNP levels were normal in in the ZG. Grade V cerebral palsy and subcortical calcification were found in 88.6% and 97.22% of children in the ZG group, respectively.
CONCLUSION
A reduction in cardiac dimensions and functional changes were found in CZS patients, based on the TAPSE, S' of the RV, and MAPSE, suggesting the importance of cardiac evaluation and follow-up in this group of patients.
Topics: Child; Humans; Female; Child, Preschool; Male; Zika Virus Infection; Cerebral Palsy; Cross-Sectional Studies; Troponin I; Echocardiography; Zika Virus
PubMed: 38019886
DOI: 10.1371/journal.pntd.0011762 -
American Journal of Medical Genetics.... Aug 2023Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we...
Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117 kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs. The differentially methylated regions (DMRs) appeared unaltered. The RTL1as gene deletion and the normal methylation pattern of the MEG3 gene loci were confirmed by methylation-specific multiplex ligation-dependent probe amplification. Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Chromosome Disorders; Genomic Imprinting; Maternal Inheritance; Phenotype; Abnormalities, Multiple; Uniparental Disomy; Chromosomes, Human, Pair 14
PubMed: 37222159
DOI: 10.1002/ajmg.a.63251 -
SAGE Open Medical Case Reports 2023Arthrogryposis multiplex congenita (AMC) is an uncommon condition present from birth that is marked by a combination of weakened muscles and multiple joint contractures....
Arthrogryposis multiplex congenita (AMC) is an uncommon condition present from birth that is marked by a combination of weakened muscles and multiple joint contractures. We present a case of a 2-year-old boy with AMC, who was born to consanguineous parents in Saudi Arabia. He presented with musculoskeletal abnormalities of all four limbs, including symmetric contractures in multiple joints of the body, bilateral developmental dysplasia of the hip, and vertical talus. Dysmorphic features included low-set ears, chin recession, triangular face, and nevus flammeus on the face. The child also had lactose intolerance, gastritis, inguinal hernia, and right-sided undescended testis. Surgical interventions were planned after a multidisciplinary team discussion. This case report highlights the good prognosis of AMC with all four-limb involvement and the importance of a thorough physical examination and a multidisciplinary approach to the diagnosis and management of AMC.
PubMed: 37771653
DOI: 10.1177/2050313X231200418