-
Clinical Genetics Jun 2024Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births....
Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.
PubMed: 38856159
DOI: 10.1111/cge.14570 -
Toxicon : Official Journal of the... Aug 2024Teratogenic plants can be found in pastures in different parts of the world and represent a threat to the reproduction of ruminants. In the northeast region of Brazil,... (Review)
Review
Teratogenic plants can be found in pastures in different parts of the world and represent a threat to the reproduction of ruminants. In the northeast region of Brazil, several studies have indicated that Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis is one of the main poisonous plants that causes reproductive problems in sheep and goats. In this context, the present study reviewed spontaneous and experimental poisonings reports by C. pyramidale in sheep and goats, as well as analyzing the phytochemical evidence related to this species. The scientific documents were retrieved from different databases and, after applying the selection criteria, a total of 16 articles published between 2000 and 2024 were included in this review. Cenostigma pyramidale causes embryonic loss, abortion, and congenital malformations in pregnant sheep and goats in the Brazilian semi-arid region. The main malformations observed in newborn animals are arthrogryposis, scoliosis, micrognathia, multiple skull deformities, cleft palate, and brachygnathism. Many secondary metabolites have already been isolated from C. pyramidale, however, to date, no evidence has been found regarding the possible teratogenic compounds that occur in this plant. From this perspective, new phytochemical studies are necessary to help unravel the mechanisms of action of embryotoxic agents from C. pyramidale.
Topics: Animals; Plant Poisoning; Brazil; Phytochemicals; Teratogens; Fabaceae; Pregnancy; Sheep; Female; Goats; Plants, Toxic; Teratogenesis; Sheep Diseases
PubMed: 38851021
DOI: 10.1016/j.toxicon.2024.107794 -
Foot & Ankle International Jun 2024Congenital Vertical Talus (CVT) is a rare form of rigid flatfoot commonly seen in patients with underlying neurologic syndromes. This study aims to evaluate the...
BACKGROUND
Congenital Vertical Talus (CVT) is a rare form of rigid flatfoot commonly seen in patients with underlying neurologic syndromes. This study aims to evaluate the long-term effectiveness of the minimally invasive method for correcting CVT deformity in a large cohort of syndromic patients.
METHODS
A single author recorded preoperative, 2-week postoperative, 1-year postoperative, and most recent radiographic measurements and complications for 25 patients treated with the minimally invasive method from 2006 to 2021. Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires were administered for 12 patients after January 1, 2015, when the institution began collecting PROMIS in all orthopaedic patients. Average follow-up was 55 months (13-111); 18 patients had minimum 24-month follow-up.
RESULTS
Forty feet in 25 patients were analyzed. The average preoperative lateral talar axis-first metatarsal base angle (TAMBA) was 68.7 ± 21.3 vs 12.1 ± 8.9 after initial surgical intervention ( < .0001). There was a statistically significant increase in the lateral TAMBA between the initial postoperative and final follow-up visits (13.0 vs 21.6, = .02). Radiographic recurrence of talonavicular deformity was noted in 12 feet (30.9%); 7 (15.55%) required corrective surgery. Larger preoperative lateral TAMBA was predictive of recurrence. Notably, patients with arthrogryposis experienced higher radiographic recurrence than other syndromic patients (45.0% vs 14.3%, = .0384). PROMIS scores were within population norms.
CONCLUSION
The study suggests that less than one-third of syndromic CVT patients experienced a radiographic recurrence of talonavicular deformity, with 15% requiring further surgical intervention at an average of 55 months following the initial procedure. A higher incidence of radiographic recurrence occurred in patients with distal arthrogryposis. These findings, along with the satisfactory patient-reported outcomes, suggest that the minimally invasive technique is an effective treatment method for syndromic CVT, underscoring the necessity for clinicians to provide detailed prognoses and consider more intensive follow-up for those at higher risk.
LEVEL OF EVIDENCE
Level IV, case series.
PubMed: 38840534
DOI: 10.1177/10711007241255116 -
Pediatric Neurology May 2024Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently,...
Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases.
BACKGROUND
Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.
METHODS
This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.
RESULTS
The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types. The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the VAMP1 (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.
CONCLUSIONS
This study contributes valuable insights into VAMP1-related CMS, emphasizing their early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.
PubMed: 38833907
DOI: 10.1016/j.pediatrneurol.2024.04.027 -
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 -
European Journal of Human Genetics :... Jun 2024STAC3 disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant...
STAC3 disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A STAC3 c.851 G > C (p.Trp284Ser) pathogenic variant, common in the Lumbee Native American tribe, has been identified in other populations worldwide, including patients of African ancestry. We report on the frequency of STAC3 c.851 G > C in a cohort of 127 patients presenting with congenital hypotonia that tested negative for spinal muscular atrophy and/or Prader-Willi syndrome. We present a clinical retrospective, descriptive review on 31 Southern African patients homozygous for STAC3 c.851 G > C. The frequencies of various phenotypic characteristics were calculated. In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3 c.851 G > C. A carrier rate of 1/56 and a predicted birth rate of 1/12 500 was estimated from a healthy cohort. A common haplotype spanning STAC3 was identified in four patients. Of the clinical group, 93% had a palatal abnormality, 52% a spinal anomaly, 59% had talipes equinovarus deformity/deformities, 38% had arthrogryposis multiplex congenita, and 22% had a history suggestive of malignant hyperthermia. The novel finding that STAC3 disorder is a common African myopathy has important clinical implications for the diagnosis, treatment and genetic counselling of individuals, with neonatal and/or childhood hypotonia with or without arthrogryposis multiplex congenita, and their families. The spread of this variant worldwide and the allele frequency higher in the African/African-American ancestry than the Admixed Americans, strongly indicates that the STAC3 c.851 G > C variant has an African origin which may be due to an ancient mutation with migration and population bottlenecks.
PubMed: 38824262
DOI: 10.1038/s41431-024-01644-5 -
Cureus Apr 2024Membranous nephropathy (MN) is an autoimmune condition that is a common cause of nephrotic syndrome in nondiabetic adults. In this study, we highlight a case of a...
Membranous nephropathy (MN) is an autoimmune condition that is a common cause of nephrotic syndrome in nondiabetic adults. In this study, we highlight a case of a 22-year-old male with a past medical history of arthrogryposis multiplex congenita (AMC) who initially presented with right flank pain and hematuria. Subsequent workup revealed significant proteinuria with biopsy-proven primary MN. Early detection of the disease is critical to establish treatment promptly and prevent complications such as those resulting from a hypercoagulable state.
PubMed: 38752080
DOI: 10.7759/cureus.58339 -
Knee Surgery, Sports Traumatology,... May 2024To assess the outcomes of medial patellofemoral ligament (MPFL) reconstruction using synthetic suture tape in paediatric patients with patellofemoral instability (PFI).
PURPOSE
To assess the outcomes of medial patellofemoral ligament (MPFL) reconstruction using synthetic suture tape in paediatric patients with patellofemoral instability (PFI).
METHODS
This ambispective comparative study, conducted from 2014 to 2022, included paediatric patients who underwent MPFL reconstruction with synthetic suture tape and had a minimum follow-up of 1 year. Pre- and postoperative clinical and functional outcomes, patient satisfaction and complications were assessed.
RESULTS
The study comprised 22 patients (29 knees), with a median age at surgery of 14.4 years (interquartile range [IQR] 10.9-16.7) and a median follow-up of 46.5 months (24.7-66). Notably, 13 knees (44.8%) had open growth plates at the time of surgery. The cohort included patients with Down syndrome (3 patients), Ehlers-Danlos (2), arthrogryposis (1), generalized joint hypermobility (8) and previous unsuccessful PFI surgeries (8). Concomitant procedures were performed on 16 knees. Postoperatively, improvements were observed in all but one patient, who reported residual pain. There were two other complications: one suture-tape rupture and one surgical wound infection. Functional scores significantly improved: Kujala, +14 points (7-29) (p < 0.001); IKDC, +10.5 points (5.2-25.3) (p < 0.001); Tegner, +2 points (0-4) (p < 0.001); Lysholm, +15 points (0-37.5) (p < 0.001). Most patients achieved excellent outcomes by Crosby-Insall criteria (21 patients, 72.4%) and reported high satisfaction (23 patients, 79.3%).
CONCLUSIONS
MPFL reconstruction using synthetic suture tape is a viable and effective treatment for paediatric patients with PFI, particularly for those with connective tissue disorders, generalized joint hypermobility or past surgical failures, significantly enhancing clinical and functional outcomes with an acceptable complication rate.
LEVEL OF EVIDENCE
Level IV.
PubMed: 38746987
DOI: 10.1002/ksa.12260 -
A retrospective study on the correction of distal arthrogryposis with a progressive extension brace.Frontiers in Pediatrics 2024Camptodactyly, clasped thumbs, and windblown hands are distinctive features of distal arthrogryposis (DA). Current therapeutic interventions often yield suboptimal...
PURPOSE
Camptodactyly, clasped thumbs, and windblown hands are distinctive features of distal arthrogryposis (DA). Current therapeutic interventions often yield suboptimal effects, predisposing patients to relapses and complications. This study explicates a corrective approach involving a progressive extension brace for the management of DA and evaluates its clinical outcomes.
METHODS
Between 2015 and 2023, progressive extension braces were used in 32 DA patients, with an average follow-up of 4.8 years. Patients were stratified by age into four groups: 0-1, 1-3, 3-7, and above 7 years. The correction of camptodactyly was assessed based on the total active movement (TAM) of metacarpophalangeal joints (MPJ) and proximal interphalangeal joints (PIPJ), as well as the extensor lag of PIPJ. Clasped thumb correction was evaluated by measuring the thumb-to-index finger metacarpal angle (M1M2 angle) and the degree of deviation at the first MPJ (M1P1 angle). The quality of life for the children was measured using PedsQL 4.0, while parental satisfaction was gauged using the FACE questionnaire.
RESULTS
Earlier intervention with a progressive extension brace yielded superior corrective results. Infants aged 0-1 year and toddlers aged 1-3 years achieved average TAM scores of 152° and 126° after correction; however, patients older than 3 years experienced a significant decrease in TAM with the same treatment. Infants and toddlers with DA showed improvement in the average extensor lag from 46° to 6°. The M1M2 angle increased from an average of 38° to 65°, with the M1P1 angle decreasing from an average of 43° to 5°. After the treatment, average PedsQL scores of 94.7 (parent-reported) and 89.3 (child-reported) were achieved. Among the 32 parents, 24 expressed high satisfaction, 5 expressed moderate satisfaction, and 3 expressed fair satisfaction.
CONCLUSION
The early, progressive, and consistent use of an extension brace significantly improved joint mobility and corrected camptodactyly and clasped thumbs. It can be an effective approach to addressing hand deformities in patients with DA.
PubMed: 38742240
DOI: 10.3389/fped.2024.1385938 -
Clinical Case Reports May 2024This current case series adds to the spectrum of Arthrogryposis renal dysfunction cholestasis (ARC)-associated variants. Increased awareness and early genetic testing...
This current case series adds to the spectrum of Arthrogryposis renal dysfunction cholestasis (ARC)-associated variants. Increased awareness and early genetic testing for ARC are suggested in cases with failure to thrive, renal tubular dysfunction, and rickets, even when the degree of cholestasis is mild. Prompt identification and intervention may improve the quality of life.
PubMed: 38698876
DOI: 10.1002/ccr3.8853