Akinesia, Arthrogryposis, Craniosynostosis: A Presentation of Neonatal Myasthenia with Fetal Onset

Cantagrel, S.; Maury, L.; Yamamoto, Anne-Marie; Maheut, J.; Toutain, Annick; Castelnau, Pierre

doi:10.1055/s-2002-34468

Cited by 11 publications

(3 citation statements)

References 7 publications

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“…8 These women can be asymptomatic, but their children are affected with severe arthrogryposis and hypotonia. [28][29][30][31][32] Almost all features-such as decreased fetal and congenital movements, arthrogryposis, facial weakness, respiratory distress, pulmonary hypoplasia, kyphosis/scoliosis, intrauterine growth retardation, faciocranial dysmorphism, low-set ears, high-arched palate, and cryptorchism-we have seen in our patients were also reported in stillbirths or newborns after intrauterine exposure to fetal AChR antibodies. [29][30][31][32] Pathogenicity of these antibodies was also demonstrated by exposing rodents to human maternal AChR antibodies.…”

Section: Discussionsupporting

confidence: 65%

Escobar Syndrome Is a Prenatal Myasthenia Caused by Disruption of the Acetylcholine Receptor Fetal γ Subunit

Hoffmann

Müller

Stricker

et al. 2006

The American Journal of Human Genetics

147

140

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Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndrome and identified eight mutations within the gamma -subunit gene (CHRNG) of the AChR. Our functional studies show that gamma -subunit mutations prevent the correct localization of the fetal AChR in human embryonic kidney-cell membranes and that the expression pattern in prenatal mice corresponds to the human clinical phenotype. AChRs have five subunits. Two alpha, one beta, and one delta subunit are always present. By switching gamma to epsilon subunits in late fetal development, fetal AChRs are gradually replaced by adult AChRs. Fetal and adult AChRs are essential for neuromuscular signal transduction. In addition, the fetal AChRs seem to be the guide for the primary encounter of axon and muscle. Because of this important function in organogenesis, human mutations in the gamma subunit were thought to be lethal, as they are in gamma -knockout mice. In contrast, many mutations in other subunits have been found to be viable but cause postnatally persisting or beginning myasthenic syndromes. We conclude that Escobar syndrome is an inherited fetal myasthenic disease that also affects neuromuscular organogenesis. Because gamma expression is restricted to early development, patients have no myasthenic symptoms later in life. This is the major difference from mutations in the other AChR subunits and the striking parallel to the symptoms found in neonates with arthrogryposis when maternal AChR auto-antibodies crossed the placenta and caused the transient inactivation of the AChR pathway.

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Section: Discussionsupporting

confidence: 65%

Escobar Syndrome Is a Prenatal Myasthenia Caused by Disruption of the Acetylcholine Receptor Fetal γ Subunit

Hoffmann

Müller

Stricker

et al. 2006

The American Journal of Human Genetics

147

140

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“…Our literature review shows that the rate of children with skeletal anomalies born from mothers with MG has been recently estimated to be around 3.9% in a cohort of 127 births,29 whereas no cases of MCC were reported in another study 31. Most authors report a high lethality of patients with AMC in the fetal or neonatal period27 29 31 32 although mild contractures or favourable skeletal outcomes are also described 27 28 33 34. Conversely, in large cohorts of fetal akinesia deformation sequence or patients with AMC, maternal AChR antibodies are either absent6 35 or found in 1.3%–7.1% of cases 36–38.…”

Section: Resultsmentioning

confidence: 85%

Diagnostic workup in children with arthrogryposis: description of practices from a single reference centre, comparison with literature and suggestion of recommendations

et al. 2021

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IntroductionArthrogryposis multiplex congenita (AMC) refers to a clinical presentation of congenital contractures involving two or more body areas. More than 400 distinct conditions may lead to AMC, making the aetiological diagnosis challenging. The objective of this work was to set up evidence-based recommendations for the diagnosis of AMC by taking advantage of both data from our nation-wide cohort of children with AMC and from the literature.Material and methodsWe conducted a retrospective single-centre observational study. Patients had been evaluated at least once at a paediatric age in the AMC clinic of Grenoble University Hospital between 2007 and 2019. After gathering data about their diagnostic procedure, a literature review was performed for each paraclinical investigation to discuss their relevance.ResultsOne hundred and twenty-five patients were included, 43% had Amyoplasia, 27% had distal arthrogryposis and 30% had other forms. A definitive aetiological diagnosis was available for 66% of cases. We recommend a two-time diagnostic process: first, non-invasive investigations that aim at classifying patients into one of the three groups, and second, selected investigations targeting a subset of patients.ConclusionThe aetiological management for patients with AMC remains arduous. This process will be facilitated by the increasing use of next-generation sequencing combined with detailed phenotyping. Invasive investigations should be avoided because of their limited yield.

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“…Clubfoot, polydactyly, craniosynostosis, and arthrogryposis are all examples of musculoskeletal defects [83]. Shear wave elastography has been used to screen for skeletal dysplasias using quantitative bone analysis [84].…”

Section: Fetal Anomalies and Need For A Screeningmentioning

confidence: 99%

Ultrasound imaging based recognition of prenatal anomalies: a systematic clinical engineering review

Sriraam,

Chinta,

Suresh

et al. 2024

Prog. Biomed. Eng.

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For prenatal screening, ultrasound imaging allows for real-time observation of developing fetal anatomy. Understanding normal and aberrant forms through extensive fetal structural assessment enables for early detection and intervention. However, the reliability of anomaly diagnosis varies depending on operator expertise and device limits. First trimester scans in conjunction with circulating biochemical markers are critical in identifying high-risk pregnancies, but they also pose technical challenges. Recent engineering advancements in automated diagnosis, such as AI-based ultrasound image processing and multimodal data fusion, are developing to improve screening efficiency, accuracy, and consistency. Still, creating trust in these data-driven solutions is necessary for integration and acceptability in clinical settings. Transparency can be promoted by explainable AI (XAI) technologies that provide visual interpretations and illustrate the underlying diagnostic decision making process. An explanatory framework based on deeplearning is suggested to construct charts depicting anomaly screening results from ultrasound video feeds. AI modeling can then be applied to these charts to connect defects with probable deformations. Overall, engineering approaches that increaseimaging, automation, and interpretability hold enormous promise for altering traditional workflows and expanding diagnostic capabilities for better prenatal care.

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Akinesia, Arthrogryposis, Craniosynostosis: A Presentation of Neonatal Myasthenia with Fetal Onset

Cited by 11 publications

References 7 publications

Escobar Syndrome Is a Prenatal Myasthenia Caused by Disruption of the Acetylcholine Receptor Fetal γ Subunit

Escobar Syndrome Is a Prenatal Myasthenia Caused by Disruption of the Acetylcholine Receptor Fetal γ Subunit

Diagnostic workup in children with arthrogryposis: description of practices from a single reference centre, comparison with literature and suggestion of recommendations

Ultrasound imaging based recognition of prenatal anomalies: a systematic clinical engineering review

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