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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 -
Prenatal Diagnosis Dec 2023Neu Laxova syndrome (NLS) is a rare and lethal congenital disorder characterized by severe intra-uterine growth retardation (IUGR), ichthyosis, abnormal facial features,...
Neu Laxova syndrome (NLS) is a rare and lethal congenital disorder characterized by severe intra-uterine growth retardation (IUGR), ichthyosis, abnormal facial features, limb abnormalities with arthrogryposis and a wide spectrum of severe malformations of the central nervous system (CNS). NLS is due to biallelic variants in three genes previously involved in serine-deficiency disorders (PHGDH, PSAT1 and PSPH), extending the phenotypic spectrum of these disorders.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Microcephaly; Fetal Growth Retardation; Ichthyosis; Phenotype
PubMed: 37964427
DOI: 10.1002/pd.6463 -
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 -
Genes May 2024Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I),...
Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. This study analyzed the clinical-genetic characteristics of patients with these conditions, focusing on both known and newly identified variants. We examined data from 15 patients, presenting symptoms of OI and joint contractures. Diagnostic methods included genealogical analysis, clinical assessments, radiography, whole exome sequencing, and direct automated Sanger sequencing. We diagnosed 15 patients with phenotypes due to biallelic variants-4 with OI Type XI, 10 with BS I, and 1 with the AG-like phenotype-demonstrating polymorphism in disease severity. Ten pathogenic variants were identified, including three novel ones, c.1373C>T (p.Pro458Leu), c.21del (p.Pro7fs), and c.831_832insCG (p.Gly278Argfs), and a recurrent variant, c.831dup (p.Gly278Argfs). Variant c.1490G>A (p.Trp497Ter) was found in two unrelated patients, causing OI XI in one and BS I in the other. Additionally, two unrelated patients with BS I and epidermolysis bullosa shared identical homozygous and variants. This observation illustrates the diversity of -related pathology and the importance of considering the full spectrum of phenotypes in clinical diagnostics.
Topics: Humans; Tacrolimus Binding Proteins; Male; Female; Arthrogryposis; Phenotype; Osteogenesis Imperfecta; Child; Child, Preschool; Pedigree; Exome Sequencing; Adolescent; Mutation; Infant; Adult; Nervous System Malformations
PubMed: 38927610
DOI: 10.3390/genes15060674 -
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 -
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 -
Psychiatric Genetics Jun 2024Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder. These variants have been identified in a group of children with...
BACKGROUND
Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder. These variants have been identified in a group of children with neurodevelopmental disorders with microcephaly, arthrogryposis, and structural brain anomalies. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes.
MATERIALS AND METHODS
For the efficient prenatal diagnosis of rare and undiagnosed diseases, the parallel detection of copy number variants (CNVs) and single nucleotide variants using whole-exome analysis is required. A physical examination of the parents was performed. Karyotype and whole-exome analysis were performed for the fetus and the parents.
RESULTS
A fetus with microcephaly and arthrogryposis; biallelic null variants (c.387-1G>A; Chr2[GRCh38]: g.130142742_130202459del) were detected by whole-exome sequencing (WES). We have reported for the first time the biallelic loss-of-function mutations in SMPD4 in patients born to unrelated parents in China.
CONCLUSION
WES could replace chromosomal microarray analysis and copy number variation sequencing as a more cost-effective genetic test for detecting CNVs and diagnosing highly heterogeneous conditions.
Topics: Humans; DNA Copy Number Variations; Exome Sequencing; Female; Prenatal Diagnosis; Sphingomyelin Phosphodiesterase; Polymorphism, Single Nucleotide; Pregnancy; Microcephaly; Heterozygote; Arthrogryposis; Male; Exome; Mutation; Neurodevelopmental Disorders
PubMed: 38690959
DOI: 10.1097/YPG.0000000000000369 -
Archives of Virology Jun 2024Akabane virus (AKAV), Aino virus, Peaton virus, Sathuperi virus, and Shamonda virus are arthropod-borne viruses belonging to the order Elliovirales, family...
Akabane virus (AKAV), Aino virus, Peaton virus, Sathuperi virus, and Shamonda virus are arthropod-borne viruses belonging to the order Elliovirales, family Peribunyaviridae, genus Orthobunyavirus. These viruses cause or may cause congenital malformations in ruminants, including hydranencephaly, poliomyelitis, and arthrogryposis, although their pathogenicity may vary among field cases. AKAV may cause relatively severe congenital lesions such as hydranencephaly in calves. Furthermore, strains of AKAV genogroups I and II exhibit different disease courses. Genogroup I strains predominantly cause postnatal viral encephalomyelitis, while genogroup II strains are primarily detected in cases of congenital malformation. However, the biological properties of AKAV and other orthobunyaviruses are insufficiently investigated in hosts in the field and in vitro. Here, we used an immortalized bovine brain cell line (FBBC-1) to investigate viral replication efficiency, cytopathogenicity, and host innate immune responses. AKAV genogroup II and Shamonda virus replicated to higher titers in FBBC-1 cells compared with the other viruses, and only AKAV caused cytopathic effects. These results may be associated with the severe congenital lesions in the brain caused by AKAV genogroup II. AKAV genogroup II strains replicated to higher titers in FBBC-1 cells than AKAV genogroup I strains, suggesting that genogroup II strains replicated more efficiently in fetal brain cells, accounting for the detection of the latter strains mainly in fetal infection cases. Therefore, FBBC-1 cells may serve as a valuable tool for investigating the virulence and tropism of the orthobunyaviruses for bovine neonatal brain tissues in vitro.
Topics: Animals; Cattle; Orthobunyavirus; Virus Replication; Brain; Cell Line; Bunyaviridae Infections; Cattle Diseases; Fetus; Cytopathogenic Effect, Viral; Immunity, Innate
PubMed: 38829449
DOI: 10.1007/s00705-024-06058-8 -
Neuromuscular Disorders : NMD Dec 2023Until recently, the disease known to be associated with THOC2 mutations was Intellectual developmental disorder, X-linked 12 (MIM300957). However, recently, fetal...
Until recently, the disease known to be associated with THOC2 mutations was Intellectual developmental disorder, X-linked 12 (MIM300957). However, recently, fetal arthrogryposis multiplex congenita has been associated with a specific splice site mutation in the THOC2 gene. We report a family with the same splice site mutation in the THOC2 gene involved in fetal arthrogryposis as well. We provide the first description of the muscular phenotype of this disease which reveals the presence of cytoplasmic bodies. Our findings expand the clinical phenotype of THOC2 gene related defects.
Topics: Humans; Arthrogryposis; Intellectual Disability; Mutation; Phenotype; RNA-Binding Proteins; RNA Splicing; Male; Infant, Newborn
PubMed: 37945483
DOI: 10.1016/j.nmd.2023.09.009