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Journal of Medical Genetics Sep 2023Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they...
BACKGROUND
Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons. Often karyotype or chromosomal microarray analyses are the only tests performed when prenatal anomalies are identified. Thereby, many cases caused by defects might be missed in the diagnostic evaluations. In this study, we aimed to dissect the most severe end of the titinopathies spectrum.
METHODS
We performed a retrospective study analysing an international cohort of 93 published and 10 unpublished cases carrying biallelic TTNtv.
RESULTS
We identified recurrent clinical features showing a significant correlation with the genotype, including fetal akinesia (up to 62%), arthrogryposis (up to 85%), facial dysmorphisms (up to 73%), joint (up to 17%), bone (up to 22%) and heart anomalies (up to 27%) resembling complex, syndromic phenotypes.
CONCLUSION
We suggest to be carefully evaluated in any diagnostic process involving patients with these prenatal signs. This step will be essential to improve diagnostic performance, expand our knowledge and optimise prenatal genetic counselling.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Connectin; Retrospective Studies; Muscle, Skeletal; Myocardium
PubMed: 36977548
DOI: 10.1136/jmg-2022-109018 -
Cureus May 2024Arthrogryposis multiplex congenita (AMC) is a rare condition characterized by multiple joint contractures at birth, affecting two or more body areas. The clinical...
Arthrogryposis multiplex congenita (AMC) is a rare condition characterized by multiple joint contractures at birth, affecting two or more body areas. The clinical examination revealed physical abnormalities indicative of AMC, including joint contractures, clubfeet, and scoliosis. The diagnostic evaluation confirmed the clinical suspicion, and prompt management was initiated to address respiratory distress and potential sepsis. Early diagnosis and multidisciplinary care are essential for optimizing outcomes in neonates with AMC. We present the case of a one-day-old neonate who exhibited immediate respiratory distress upon birth and was born via a lower segment cesarean section (LSCS) to a 31-year-old mother. This case underscores the importance of recognizing prenatal ultrasound findings suggestive of AMC and implementing appropriate postnatal care strategies for affected neonates. Early diagnosis and multidisciplinary care are essential for optimizing outcomes in neonates with AMC.
PubMed: 38903284
DOI: 10.7759/cureus.60729 -
PloS One 2023Feed efficiency is a major constraint in the beef industry and has a significant negative correlation with residual feed intake (RFI). RFI is widely used as a measure of...
Feed efficiency is a major constraint in the beef industry and has a significant negative correlation with residual feed intake (RFI). RFI is widely used as a measure of feed efficiency in beef cattle and is independent of economic traits such as body weight and average daily gain. However, key traits with commonality or specificity among beef cattle breeds at the same level of RFI have not been reported. Accordingly, the present study hypothesized that signatures associated with feed efficiency would have commonality or specificity in the liver of cattle breeds at the same RFI level. By comparing and integrating liver transcriptome data, we investigated the critical signatures closely associated with RFI in beef cattle using weighted co-expression network analysis, consensus module analysis, functional enrichment analysis and protein network interaction analysis. The results showed that the consensus modules in Angus and Charolais cattle were negatively correlated, and four (turquoise, red, tan, yellow) were significantly positively correlated in Angus liver, while (turquoise, red) were significantly negatively correlated in Charolais liver. These consensus modules were found to be primarily involved in biological processes such as substance metabolism, energy metabolism and gene transcription, which may be one of the possible explanations for the difference in feed efficiency between the two beef breeds. This research also identified five key candidate genes, PLA2G12B, LCAT, MTTP, LCAT, ABCA1 and FADS1, which are closely associated with hepatic lipid metabolism. The present study has identified some modules, genes and pathways that may be the major contributors to the variation in feed efficiency among different cattle breeds, providing a new perspective on the molecular mechanisms of feed efficiency in beef cattle and a research basis for investigating molecular markers associated with feed efficiency in beef cattle.
Topics: Animals; Cattle; Liver; Arthrogryposis; Consensus; Data Interpretation, Statistical; Eating
PubMed: 37756351
DOI: 10.1371/journal.pone.0289939 -
Orphanet Journal of Rare Diseases Jun 2024Arthrogryposis multiplex congenita (AMC) is a group of rare musculoskeletal conditions that is associated with complex healthcare needs and long-term follow up. The...
BACKGROUND
Arthrogryposis multiplex congenita (AMC) is a group of rare musculoskeletal conditions that is associated with complex healthcare needs and long-term follow up. The literature reports significant direct, indirect, and psychosocial costs for caregivers of children with neuromuscular conditions. Due to mobility limitations and frequent hospital visits, caring for a child with AMC is complex. Other challenges experienced by caregivers include financial strain, job changes, changes in interpersonal relationships and abandonment. This study was aimed at exploring the lived experience of caregivers of children with AMC.
METHODS
The present study is part of a larger global mixed methods study. In the initial quantitative aspect of the study, caregivers (n = 158) of children and youths with AMC (aged 0-21 years) responded to a cost of care survey on an electronic platform. Of the 158 participants, 13 caregivers then further consented to participate in the qualitative aspect of the study in which a 60-min semi-structured, individual interview was conducted remotely. Open-ended questions were developed to gain a deeper understanding of the direct and indirect costs of care, their impact on the caregivers' lives and the quality of the care-giving experience. Interviews were transcribed, and a coding scheme was developed drawing from both the existing literature and the content of the interviews. A deductive and inductive thematic analysis was used to analyze the qualitative data using the NVivo® qualitative data analysis software.
RESULTS AND CONCLUSION
Five themes describing the experiences of caregivers of children with AMC emerged from the analysis of the qualitative data: 1. Impact of the caregiving experience; 2. Cost of childcare; 3. Support system for care; 4. Managing and navigating care; 5. Supporting the child's growth and development. In addition to the results of the thematic analysis, specific recommendations shared by the caregivers included the need for support groups and provision of support to youths to prepare them for adolescence. These findings will inform resource allocation, policymaking, and support services for children with rare conditions, their caregivers and families.
Topics: Humans; Arthrogryposis; Caregivers; Child; Adolescent; Female; Male; Child, Preschool; Infant; Young Adult; Adult; Rare Diseases; Qualitative Research; Infant, Newborn; Musculoskeletal Diseases
PubMed: 38877508
DOI: 10.1186/s13023-024-03224-8 -
Clinical Case Reports Jul 2023Lethal multiple pterygium syndrome is a very rare genetic disorder. The manifestations of this condition include growth deficiency of the fetus, craniofacial anomalies,...
Lethal multiple pterygium syndrome is a very rare genetic disorder. The manifestations of this condition include growth deficiency of the fetus, craniofacial anomalies, joint contracture, and skin webbing (pterygia). This disorder is fatal before birth or shortly after birth. We reported a case of lethal multiple pterygium syndrome with multiple anomalies including pterygia involving the axilla, bilateral antecubital fossa, and groin. Arthrogryposis involving multiple lower and upper extremities joints. Cleft palate, microstomia and limitation of mouth opening, webbed neck, asymmetric small and narrow chest, ambiguous genitalia, depressed and wide nasal bridge, antemongoloid slant, low-set, malformed, and posteriorly rotated ears, pterygia, syndactyly and camptodactyly of hands and rocket bottom feet. LMPS is a congenital genetic disease with multiple anomalies that is fatal in the second and third trimesters of pregnancy or shortly after birth. With genetic testing and counseling, it can be prevented from recurring in subsequent pregnancies.
PubMed: 37448946
DOI: 10.1002/ccr3.7678 -
Research Involvement and Engagement Aug 2023Upper extremity (UE) involvement is prevalent in 73% of individuals with arthrogryposis multiplex congenita (AMC), yet no AMC-specific outcome measure exists. When...
BACKGROUND
Upper extremity (UE) involvement is prevalent in 73% of individuals with arthrogryposis multiplex congenita (AMC), yet no AMC-specific outcome measure exists. When developing a measure specific to a population with a rare musculoskeletal condition, clinicians' and patients' perspectives and involvement is a crucial and necessary step. This study sought to determine the most clinically useful items for an outcome measure of UE function for children with AMC as defined by caregivers and clinicians.
METHODS
To ensure the perspectives and needs of caregivers of children with AMC and clinicians were considered in the development of the UE measure for AMC, a Nominal Group technique (NGT) with caregivers of children with AMC (phase 1) followed by a three-round survey with clinicians (phase 2) were carried out.
RESULTS
Phase 1: Eleven individuals participated in the nominal group technique and identified 32 items. The most important items were Picking up an object (n = 11), Eating (n = 10), Reaching mouth (n = 10), Getting out of bed (n = 10). Phase 2: Invitations to participate to an online survey was sent to 47 experts in the field of AMC, 20 participants completed round 1, 15 completed round 2 and 13 completed round 3. Throughout the survey, participants were asked about movement required to screen the UE, essential domains to be included in the measure, establishing a scoring guide and identifying tasks associated with joint motion and position.
CONCLUSION
A preliminary version of an UE AMC-specific outcome measure was developed with the help of caregivers' perspectives and expert opinions.
PubMed: 37553603
DOI: 10.1186/s40900-023-00479-6 -
Acta Ortopedica Brasileira 2023The genu recurvatum is characterized by a hyperextension deformity of the knee in the sagittal plane. Among its causes are conditions such as arthrogryposis, cerebral...
INTRODUCTION
The genu recurvatum is characterized by a hyperextension deformity of the knee in the sagittal plane. Among its causes are conditions such as arthrogryposis, cerebral palsy, poliomyelitis, sequelae of tibial tuberosity fracture and some syndromes with generalized joint hypermobility. Treatment of this deformity can be challenging and, to date, aggressive methods such as femur or tibial osteotomies are the most used for its correction.
OBJECTIVE
This study aimed to describe a new surgical technique for correcting genu recurvatum.
METHODS
This is a prospective clinical study of children who underwent posterior hemiepiphysiodesis of the distal femur with transphyseal screws.
RESULTS
The approach proved to be safe and useful for genu recurvatum deformities, with femoral or articular apex.
CONCLUSION
This approach shows great potential for correcting genu recurvatum in the developing skeleton, being an excellent alternative to the more aggressive methods currently used to treat this deformity.
PubMed: 38115875
DOI: 10.1590/1413-785220233105e268307 -
Journal of Children's Orthopaedics Feb 2024The aim of this systematic review was to address the Ponseti method in arthrogrypotic clubfoot treatment and evaluate the success, complication, and recurrence rates. (Review)
Review
PURPOSE
The aim of this systematic review was to address the Ponseti method in arthrogrypotic clubfoot treatment and evaluate the success, complication, and recurrence rates.
METHOD
A systematic review was performed in the PubMed, Scopus, Embase, and Web of Science databases on 9 January 2023, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Success, recurrence, and complication rates were evaluated and analyzed. Risks of bias and the quality of the studies were also evaluated.
RESULTS
Five case series, including 53 patients (102 feet), were identified. According to this model, the initial success rate was 91% (95% confidence interval = 0.79-0.96) with = 43%, and the final success was 68% (at 5.8 years of follow-up). Recurrence rate was 30% (95% confidence interval = 0.14-0.52).
CONCLUSION
Ponseti method is indicated in the initial treatment of arthrogrypotic clubfeet, as it is a minimally invasive method with a high correction rate (91%). However, a high recurrence rate (30%) requires early detection and adequate treatment.
LEVEL OF EVIDENCE
Level III.
PROSPERO PROTOCOL
CRD42020210373.
PubMed: 38348434
DOI: 10.1177/18632521231214778 -
JPMA. the Journal of the Pakistan... Nov 2023Foetal akinesia deformation sequence (FADS) represents a group of disorders resulting from absent or diminished in utero foetal mobility. The aetiology is...
Foetal akinesia deformation sequence (FADS) represents a group of disorders resulting from absent or diminished in utero foetal mobility. The aetiology is multifactorial, including genetic, environmental, maternal, and foetal causes. The absence of foetal movements leading to multiple joint contractures, pulmonary hypoplasia, and intrauterine growth restriction are the key features of foetal akinesia deformation sequence. Herein we describe the case of a 30-year-old gravida 4 (para 2+1) who came for foetal ultrasound at 28 weeks of gestation due to decreased foetal movements. Ultrasound showed features of FADS with fixed flexed position of foetal limbs, pulmonary hypoplasia, polyhydramnios, and intrauterine growth restriction. The timely use of ultrasound enables early detection of these cases and aids in appropriate counselling and management.
Topics: Pregnancy; Female; Humans; Adult; Fetal Growth Retardation; Arthrogryposis; Contracture; Ultrasonography, Prenatal
PubMed: 38013544
DOI: 10.47391/JPMA.8513 -
Orphanet Journal of Rare Diseases Aug 2023Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and...
BACKGROUND
Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca.
METHODS
The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed.
RESULTS
A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin.
CONCLUSIONS
In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.
Topics: Female; Humans; Male; Amyloid Neuropathies, Familial; Arthrogryposis; Heterozygote
PubMed: 37653545
DOI: 10.1186/s13023-023-02865-5