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International Journal of Rare Diseases... 2021Falls research among individuals with arthrogryposis multiplex congenita (AMC), a group of congenital conditions characterized by joint contractures in two or more body...
BACKGROUND
Falls research among individuals with arthrogryposis multiplex congenita (AMC), a group of congenital conditions characterized by joint contractures in two or more body regions, is sparse. The primary objectives of this study were to estimate the prevalence of single, multiple, and injurious falls among adolescents and adults with AMC and identify factors associated with multiple and injurious falls.
METHODS
Individuals, aged 10-50 years, with a diagnosis of AMC completed questionnaires obtaining demographic and AMC-specific information, falls history (e.g., number, injurious/non-injurious), markers of bone health, orthopedic surgical history, and mobility aid use, as well as the Gillette Functional Assessment Questionnaire and the Saltin-Grimby Physical Activity Level Scale. Falls were defined as "any body part above the ankle coming to rest on the ground, floor, or a lower level". Falling was defined as ≥ 1 fall, while multiple falls were defined as ≥ 2 falls in the past year.Differences in falling, multiple falls, and injurious falls rates between adolescents (10-17 years) and adults (aged 18-50 years) were evaluated. Using univariate binary logistic regression models, associations between participant characteristics and multiple falls, as well as injurious falls, were evaluated, while considering age as a covariate (p ≤ 0.050); odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
RESULTS
Adolescents (N = 28; median age = 14 years) and adults (N = 40; median age = 32 years) with AMC had similar falling, i.e., 89.3% versus 70.0%, and injurious fall rates, i.e., 32.1% versus 27.5%, respectively (p > 0.050).Adolescents with AMC, however, were more likely to report multiple falls in the past year, i.e., 89.3%, when compared to adults with AMC, i.e., 57.5% (p = 0.005). Beyond age, multiple falls were associated with a greater number of lower-limb surgeries [p = 0.036, OR (95%CI): 1.18 (1.01-1.39)], ability to transfer floor-to-stand with support [p = 0.002, OR (95%CI): 8.98 (2.30-35.06)], and increased mobility per the Gillette Functional Assessment Questionnaire [p = 0.004, OR (95%CI): 1.48 (1.13-1.92)]. Factors associated with a reduced odds of multiple falls were spinal involvement [p = 0.025, OR (95%CI): 0.23 (0.07-0.84)], history of spinal surgery [p = 0.018, OR (95%CI: 0.18 (0.04-0.74)], greater upper extremity involvement [OR (95%CI): 0.65 (0.44-0.95)], home assistive device use [p = 0.010, OR (95%CI): 0.15 (0.03-0.63)], and community wheelchair use [p = 0.006, OR (95%CI): 0.16 (0.04-0.59)]. None of the explored characteristics were associated with injurious falls in the past year (p > 0.050).
CONCLUSION
Falls are exceedingly common among adolescents and adults with AMC; potential risk and protective factors for multiple falls are identified for future prospective falls research.
PubMed: 34723192
DOI: 10.23937/2643-4571/1710035 -
Pediatric Neurology Sep 2020Intrauterine Zika virus infection is associated with neurological disorders and other problems, including such as impaired visual and hearing function and orthopedic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrauterine Zika virus infection is associated with neurological disorders and other problems, including such as impaired visual and hearing function and orthopedic abnormalities, including arthrogryposis. We systematically investigated the prevalence of arthrogryposis in infants with congenital Zika syndrome and the respective risk of mortality.
METHODS
We conducted a systematic review and meta-analysis of reports published in PubMed, Web of Science, SCOPUS, and World Health Organization Global Index Medicus databases, using the keywords Zika virus and arthrogryposis and related terms.
RESULTS
After screening titles and abstracts, a total of four studies were included. Arthrogryposis was not associated with increased risk for fetal demise (risk ratio, 3.33; 95% confidence interval, 0.73 to 15.26). However, arthrogryposis was associated with a 13-fold increased risk of mortality in neonates with congenital Zika syndrome (risk ratio, 13.11; 95% confidence interval, 3.74 to 45.92) than neonates with congenital Zika syndrome but without arthrogryposis.
CONCLUSIONS
Neonates with both congenital Zika syndrome and arthrogryposis had higher morbidity and mortality risks, making it necessary to implement protocols for the early identification of neuromuscular changes and appropriate management of patients.
Topics: Arthrogryposis; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Zika Virus Infection
PubMed: 32646676
DOI: 10.1016/j.pediatrneurol.2020.05.007 -
Animals : An Open Access Journal From... Sep 2020Arthrogryposis and macroglossia are congenital pathologies known in several cattle breeds, including Piemontese. As variations in single genes were identified as...
Arthrogryposis and macroglossia are congenital pathologies known in several cattle breeds, including Piemontese. As variations in single genes were identified as responsible for arthrogryposis in some breeds, we decided: (i) to test the hypothesis of a similar genetic determinism for arthrogryposis in the Piemontese breed by genotyping affected and healthy animals with a high-density chip and applying genome-wide association study (GWAS), and canonical discriminant analysis (CDA) procedures, and (ii) to investigate with the same approach the genetic background of macroglossia, for which no genetic studies exist so far. The study included 125 animals (63 healthy, 30 with arthrogryposis, and 32 with macroglossia). Differently from what reported for other breeds, the analysis did not evidence a single strong association with the two pathologies. Rather, 23 significant markers on different chromosomes were found (7 associated to arthrogryposis, 11 to macroglossia, and 5 to both pathologies), suggesting a multifactorial genetic mechanism underlying both diseases in the Piemontese breed. In the 100-kb interval surrounding the significant SNPs, 20 and 26 genes were identified for arthrogryposis and macroglossia, respectively, with 12 genes in common to both diseases. For some genes (, , , and ), a possible role in the pathologies can be hypothesized, being involved in processes related to muscular or nervous tissue development. The real involvement of these genes needs to be further investigated and validated.
PubMed: 32987629
DOI: 10.3390/ani10101732 -
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 -
Neurogenetics Jan 2024Sphingomyelin phosphodiesterase 4 (SMPD4) encodes a member of the Mg-dependent, neutral sphingomyelinase family that catalyzes the hydrolysis of the phosphodiester bond... (Review)
Review
Sphingomyelin phosphodiesterase 4 (SMPD4) encodes a member of the Mg-dependent, neutral sphingomyelinase family that catalyzes the hydrolysis of the phosphodiester bond of sphingomyelin to form phosphorylcholine and ceramide. Recent studies have revealed that biallelic loss-of-function variants of SMPD4 cause syndromic neurodevelopmental disorders characterized by microcephaly, congenital arthrogryposis, and structural brain anomalies. In this study, three novel loss-of-function SMPD4 variants were identified using exome sequencing (ES) in two independent patients with developmental delays, microcephaly, seizures, and brain structural abnormalities. Patient 1 had a homozygous c.740_741del, p.(Val247Glufs*21) variant and showed profound intellectual disability, hepatomegaly, a simplified gyral pattern, and a thin corpus callosum without congenital dysmorphic features. Patient 2 had a compound heterozygous nonsense c.2124_2125del, p.(Phe709*) variant and splice site c.1188+2dup variant. RNA analysis revealed that the c.1188+2dup variant caused exon 13 skipping, leading to a frameshift (p.Ala406Ser*6). In vitro transcription analysis using minigene system suggested that mRNA transcribed from mutant allele may be degraded by nonsense-mediated mRNA decay system. He exhibited diverse manifestations, including growth defects, muscle hypotonia, respiratory distress, arthrogryposis, insulin-dependent diabetes mellitus, sensorineural hearing loss, facial dysmorphism, and various brain abnormalities, including cerebral atrophy, hypomyelination, and cerebellar hypoplasia. Here, we review previous literatures and discuss the phenotypic diversity of SMPD4-related disorders.
Topics: Male; Humans; Microcephaly; Arthrogryposis; Neurodevelopmental Disorders; Nervous System Malformations; Intellectual Disability; Cerebellum
PubMed: 37882972
DOI: 10.1007/s10048-023-00737-5 -
BMC Medical Genomics Mar 2021Cerebro-oculo-facio-skeletal syndrome (COFS) is a severe and progressive neurologic condition characterized by prenatal onset of arthrogryposis, cataract, microcephaly...
BACKGROUND
Cerebro-oculo-facio-skeletal syndrome (COFS) is a severe and progressive neurologic condition characterized by prenatal onset of arthrogryposis, cataract, microcephaly and growth failure. The aim of this study was to present a case of recurrence of the COFS syndrome and to propose a differential diagnosis flow-chart in case of prenatal findings of arthrogryposis and cataract.
CASE PRESENTATION
We report a case of recurrence of COFS3 syndrome within the same family, with similar diagnostic features. In the first case the COFS syndrome remained undiagnosed, while in the second case, due to prenatal findings of arthrogryposis and cataract, genetic investigation focusing on responsible genes of COFS (ERCC5, ERCC6 and FKTN genes) was carried out. The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.
CONCLUSION
COFS syndrome is a rare autosomic recessive condition. However, it can be suspected and diagnosed prenatally. The flow-chart illustrates a pathway to guide differential diagnosis according to the prenatal findings. Main syndromes, key testing and specific genes are included. Targeted molecular testing should be offered to the couple in order to reach a diagnosis and assess the recurrence risk for future pregnancies.
Topics: Adult; Arthrogryposis; Cockayne Syndrome; Diagnosis, Differential; Female; Humans; Pregnancy
PubMed: 33766032
DOI: 10.1186/s12920-021-00939-6 -
Science (New York, N.Y.) Jan 2023Dysfunction of a mechanosensor in sensory neurons causes joint contracture.
Dysfunction of a mechanosensor in sensory neurons causes joint contracture.
Topics: Humans; Arthrogryposis; Mechanotransduction, Cellular; Sensory Receptor Cells; Ion Channels; Animals; Mice; Disease Models, Animal
PubMed: 36634168
DOI: 10.1126/science.adf6570 -
Fetal Diagnosis and Therapy 2022Bruck syndrome is a rare autosomal recessive disease characterized by multiple joint contractures, bone fragility, and fractures. Two genes have been associated with...
INTRODUCTION
Bruck syndrome is a rare autosomal recessive disease characterized by multiple joint contractures, bone fragility, and fractures. Two genes have been associated with Bruck syndrome, FKBP10 and PLOD2, though they are phenotypically indistinguishable.
CASE PRESENTATION
We present a prenatally diagnosed case of Bruck syndrome in a young multiparous woman, with no notable personal, family or obstetric history. A 12-week ultrasound raised the suspicion of short long bones, subsequently confirmed at 16 weeks. In addition, bilateral fixed flexion of the elbow, wrist, and knee joints as well as talipes was observed. Chromosomal SNP microarray analysis (0.2 Mb) detected a homozygous deletion at chromosome 3, band q24, involving a part of PLOD2 to a part of PLSCR4. At mid-trimester morphology, bilateral intrauterine fractures of the humerus and femur were evident. In the late third trimester, a fetal echocardiogram noted enlargement of the right heart with severe tricuspid regurgitation in combination with pulmonary insufficiency and a restrictive arterial duct. The potential risk of premature closure of the ductus arteriosus near term led to delivery by emergency caesarean section.
CONCLUSION
To our knowledge, this is the first case of Bruck syndrome prenatally confirmed by chromosomal microarray analysis and the second reported case with an extra-skeletal abnormality. This case highlights the importance of comprehensive fetal morphological assessment during pregnancy as diagnosis of an additional abnormality has the potential to impact both management and prognosis.
Topics: Humans; Pregnancy; Female; Arthrogryposis; Homozygote; Cesarean Section; Sequence Deletion; Osteogenesis Imperfecta; Phospholipid Transfer Proteins
PubMed: 36476632
DOI: 10.1159/000527594 -
Journal of AAPOS : the Official... Apr 2022Wieacker-Wolff syndrome is an X-linked condition caused by variants of the ZC4H2 gene that results in in utero muscular weakness that manifests clinically as...
Wieacker-Wolff syndrome is an X-linked condition caused by variants of the ZC4H2 gene that results in in utero muscular weakness that manifests clinically as arthrogryposis congenita as well as facial and bulbar weakness. We report the case of a young girl with a de novo pathogenic deletion in the ZC4H2 gene and clinical features consistent with Wieacker-Wolff syndrome. Common eye manifestations of the syndrome reported in the literature include ptosis, strabismus, and oculomotor apraxia. The overall incidence of these manifestations is 56%.
Topics: Apraxias; Contracture; Female; Genetic Diseases, X-Linked; Humans; Intracellular Signaling Peptides and Proteins; Muscular Atrophy; Nuclear Proteins; Ophthalmoplegia
PubMed: 35121145
DOI: 10.1016/j.jaapos.2021.10.010 -
Brain & Development Oct 2023Variants of SCN1A represent the archetypal channelopathy associated with several epilepsy syndromes. The clinical phenotypes have recently expanded from Dravet syndrome....
Variants of SCN1A represent the archetypal channelopathy associated with several epilepsy syndromes. The clinical phenotypes have recently expanded from Dravet syndrome. CASE REPORT: We present a female patient with the de novo SCN1A missense variant, c.5340G > A (p. Met1780Ile). The patient had various clinical features with neonatal onset SCN1A epileptic encephalopathy, arthrogryposis multiplex congenita, thoracic hypoplasia, thoracic scoliosis, and hyperekplexia. CONCLUSION: Our findings are compatible with neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis; the most severe phenotype probably caused by gain-of-function variant of SCN1A. The efficacy of sodium channel blocker was also discussed. Further exploration of the phenotype-genotype relationship of SCN1A variants may lead to better pharmacological treatments and family guidance.
Topics: Female; Humans; Arthrogryposis; Epilepsies, Myoclonic; Mutation, Missense; Epileptic Syndromes; Movement Disorders; Phenotype; NAV1.1 Voltage-Gated Sodium Channel; Mutation
PubMed: 37442734
DOI: 10.1016/j.braindev.2023.06.009