Miopatía miotubular ligada al cromosoma X: informe clínico y revisión del fenotipo leve / X-linked myotubular myopathy: a clinical report and a review of the mild phenotype

Introducción: La miopatía miotubular ligada al X es una miopatía centronuclear rara que afecta aproximadamente a 1 de cada 50.000 recién nacidos varones causada por variantes patógenas en el gen de la miotubularina 1 (MTM1). La gravedad clínica varía; sin embargo, la necesidad de soporte ventilatorio ocurre casi invariablemente. Caso clínico: Presentamos el caso de un niño de 4 años que presentaba hipotonía muscular leve a los 12 meses, trastorno del lenguaje expresivo, retraso global del desarrollo y trastorno del procesamiento sensorial. La secuenciación clínica del exoma identificó la variante hemicigótica c.722G>A p.(Arg241His) en el exón 9 del gen de la miotubularina 1 (NM_000252.2). La madre es portadora heterocigota de la misma variante. Se estableció el diagnóstico de una forma leve de miopatía miotubular ligada al cromosoma X de herencia materna. El niño presentó una mejoría significativa con terapias del habla, ocupacional y física, sin intercurrencias respiratorias ni dependencia de ventilador. Conclusión: La presentación de una forma leve de esta miopatía miotubular, al notificarse más raramente, añadió desafío al diagnóstico. La combinación de hipotonía leve, dificultades de alimentación y trastorno del lenguaje expresivo debe hacer sospechar una enfermedad neuromuscular. Se carece de puntuaciones motoras o de desarrollo verificadas específicas de esta miopatía para determinar el pronóstico y la necesidad de otras terapias. Aunque actualmente la gravedad de la miopatía miotubular se clasifica según la dependencia del ventilador, esto puede ser insuficiente e inaplicable a los casos más leves. Es evidente la necesidad de un sistema de clasificación para los casos leves y moderados que evalúe la debilidad muscular y la fatiga, las limitaciones de la vida diaria, el retraso del desarrollo motor, las puntuaciones fenotípicas tempranas o las infecciones respiratorias recurrentes.(AU)

Introduction: X-linked myotubular myopathy is a rare centronuclear myopathy that affects approximately 1 in 50,000 male newborns caused by pathogenic variants in the myotubularin 1 gene (MTM1). The clinical severity varies, however the need for ventilatory support occurs almost invariably. Case report: We report the case of a 4-year-old boy presenting mild muscle hypotonia at 12 months-old, expressive language disorder, global developmental delay, and a sensory processing disorder. Clinical exome sequencing identified the hemizygous variant c.722G>A p.(Arg241His) in exon 9 of the myotubularin 1 gene (NM_000252.2). The mother is a heterozygous carrier of the same variant. A diagnosis of a mild form of maternal inherited X-linked myotubular myopathy was established. The child presented significant improvement with speech, occupational, and physical therapies, with no respiratory intercurrences or ventilator dependency. Conclusion: The presentation of a mild form of this myotubular myopathy, being less commonly reported, added challenge to the diagnosis. The combination of mild hypotonia, feeding difficulties and expressive language disorder should raise suspicion of a neuromuscular disease. There is a lack of verified motor or developmental scores specific to this myopathy to further determine prognosis and need of other therapies. While currently the severity myotubular myopathy is classified according to ventilator dependency, this may be insufficient and unapplicable to milder cases. There is an evident need for a grading system for mild and moderate cases assessing muscle weakness and fatigue, daily life limitations, motor developmental delay, early phenotypical scores, or recurrent respiratory infections.(AU)

Terapia miofuncional orofacial associada ao uso da placa palatina de memória em crianças com Trissomia do 21: estudo de casos / Orofacial myofunctional therapy associated with the use of the stimulating palatal plate in children with trisomy 21: case studies

RESUMO Indivíduos com Trissomia do 21 podem apresentar hipotonia muscular dos órgãos fonoarticulatórios, língua alargada, posicionada no assoalho oral e protrusa e ausência de selamento labial. A placa palatina de memória é um dispositivo intraoral que, associado à terapia miofuncional, visa à melhora da postura habitual dos lábios e da língua dessas crianças. O objetivo deste trabalho foi apresentar os casos de quatro crianças com Trissomia do 21, do sexo masculino, com média de idade de 6,7 e desvio-padrão de 7,8 meses, que fizeram uso da placa palatina de memória de forma associada à terapia miofuncional. As crianças utilizaram a placa por seis meses, realizaram exercícios baseados na terapia de regulação orofacial e receberam orientações quanto à alimentação e retirada de hábitos orais deletérios. Na primeira sessão e ao final do tratamento, foi realizada a gravação de 5 minutos da face de cada criança em repouso e a análise da postura habitual de língua e de lábios foi realizada por dois pesquisadores independentes. Observou-se maior melhora da postura de língua e de lábios dos participantes que iniciaram o tratamento mais precocemente e que apresentavam as alterações posturais mais severas.

ABSTRACT Individuals with trisomy 21 may have muscle hypotonia of the speech articulation organs, an enlarged protruding tongue positioned on the floor of the mouth, and a lack of lip closure. The stimulating palatal plate is an intraoral appliance that, associated with myofunctional therapy, aims to improve these children's habitual lip and tongue posture. This study aimed to present the cases of four male children with trisomy 21, with a mean age of 6.7 and a standard deviation of 7.8 months, who used the stimulating palatal plate in association with myofunctional therapy. The children used the plate for 6 months and did exercises based on the orofacial regulation therapy, and their parents received instructions on feeding them and removing deleterious oral habits. In the first session and at the end of the treatment, each child's face was video-recorded for 5 minutes at rest, and two researchers analyzed independently their habitual tongue and lip posture. Participants who began the treatment earlier and had the most severe postural changes had greater tongue and lip posture improvement.

Wrist-ankle acupuncture combined with rehabilitation for dysphagia caused by achalasia of cricopharyngeal muscle after stroke / 中国基层医药

Objective:To investigate the clinical efficacy of wrist-ankle acupuncture combined with rehabilitation for dysphagia caused by achalasia of the cricopharyngeal muscle after stroke.Methods:Sixty patients with dysphagia caused by achalasia of the cricopharyngeal muscle after stroke who received treatment in Wenzhou Hospital of Traditional Chinese Medicine from June 2019 to March 2020 were included in this study. They were randomly divided into a treatment group and a control group ( n = 30). All patients received routine drug treatment and swallowing rehabilitation training. The control group underwent routine acupuncture treatment. The treatment group received wrist-ankle acupuncture based on routine acupuncture treatment. Both groups were treated for 4 consecutive weeks. The clinical efficacy in the two groups was evaluated using the Video Fluoroscopic Swallowing Study (VFSS), Standardized Swallowing Assessment (SSA), and Swallow Quality-of-Life Questionnaire (SWAL-QOL). Results:Before treatment, there were no significant differences in VFSS, SSA, and SWAL-QOL scores between the two groups. After treatment, VFSS, SSA, and SWAL-QOL scores in the treatment group were (8.21 ± 0.77) points, (21.19 ± 1.42) points, (200.24 ± 11.12) points, and they were (6.01 ± 0.36) points, (23.31 ± 1.45) points, and (182.37 ± 12.06) points in the control group ( t = 3.26, 5.50, 6.31, all P < 0.05). Conclusion:Wrist-ankle acupuncture combined with rehabilitation is an effective treatment method for dysphagia caused by achalasia of the cricopharyngeal muscle after stroke. It can alleviate dysphagia and improve quality of life.

Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations.

Infantile neuroaxonal dystrophy (INAD) is a rare recessive neurodegenerative disorder manifested by symptoms like hypotonia, extrapyramidal signs, spastic tetraplegia, vision problems, cerebellar ataxia, cognitive complications, and dementia before the age of three. Various reports evaluated the relationship between the incidence of INAD and different mutations in the PLA2G6 gene. We described cases of two children with INAD whose diagnoses were challenging due to misleading findings and a mutation in the C.2370 T>G (p. Y790X) in the PLA2G6 gene based on NM_001349864, which has been reported previously.

Down syndrome: orofacial pain, masticatory muscle hypotonia, and sleep disorders.

The aim of the present study was to investigate orofacial pain in individuals with Down syndrome (DS) and determine possible associations with masticatory muscle hypotonia (MMH), maximum mouth opening (MMO), and sleep disorders. Twenty-three individuals with DS underwent a standardized clinical examination using Axis I of the Diagnostic Criteria for Temporomandibular Disorders, for the diagnosis of pain in the masseter and temporal muscles and temporomandibular joint (TMJ). MMH was investigated using electromyography of the temporal and masseter muscles and the measurement of maximum bite force (MBF). MMO was measured using an analog caliper. Sleep disorders (obstructive sleep apnea [OSA], snoring index [SI], and sleep bruxism index [SBI]) were investigated using type II polysomnography. Statistical analysis was performed. Nonsignificant differences were found in muscle and TMJ pain between the sexes. However, myalgia and referred myofascial pain in the left masseter muscle were more frequent in males (69%) than females (40%). Electrical activity of the temporal (left: p = .002; right: p = .004) and masseter (left: p = .008) muscles was significantly lower in males than in females. MBF range was lower in males than females, indicating the highest MMH among males. OSA, SI, and SBI were identified in both sexes, but with no statistically significant differences. We concluded that myalgia and referred myofascial pain were found in some individuals with DS, especially in males. Arthralgia was found mainly in females. Temporal and masseter myalgia may have exerted an influence on the severity of MMH in males, particularly on the left side.

A Cohen syndrome patient whose muscle-relaxant effect may have been prolonged during general anesthesia: a case report.

Cohen syndrome is a rare genetic disorder associated with mutations in the VPS13B gene. Individuals with this disorder present with diverse clinical manifestations, including muscle hypotonia, intellectual disabilities, and typical facial characteristics, such as prominent upper central incisors and micrognathia. General anesthesia was administered to a 23-year-old man with Cohen syndrome. Although we observed prominent upper central incisors, an overjet of 10 mm, micrognathia, and thyromental distance of 4 cm, hypotonia was not observed in the patient. Intubation was rendered difficult when performing a direct laryngoscopy. However, smooth intubation was achieved using a video laryngoscope. The patient's train of four (TOF) count remained zero close to 60 min after rocuronium administration, suggesting that the drug's muscle-relaxant effect may have been prolonged. A TOF ratio of 0.79 was confirmed 130 min after rocuronium administration, and a TOF ratio of 1.0 was confirmed after administration of 150 mg of sugammadex. The patient's respiration remained stable after extubation, and no recurarization of muscle relaxation was observed. As demonstrated in this case report, it is important to closely monitor recovery from muscle relaxation and prepare multiple techniques for airway management in general anesthesia management of patients with Cohen syndrome.

Electromyographic Study of Masticatory Muscle Function in Children with Down Syndrome.

This study assessed the electrical activity of the masticatory muscles in both children with down syndrome (DS) and healthy children. After applying the inclusion and exclusion criteria, 30 patients aged between 7.9 and 11.8 years participated in the study. They were divided into two groups of 15: DS and non-DS. A DAB-Bluetooth device (Zebris Medical GmbH, Germany) was used to record the electromyographical (EMG) activity of the right and left temporal and of the right and left masseter muscles at rest and during maximum voluntary clenching (MVC). The asymmetry index between right and left masticatory muscle EMG activity was calculated for each position. The Mann-Whitney U test was applied to analyze the study results. There were no differences in the electrical activity of the temporal and masseter muscles at rest between the groups. During MVC, the asymmetry index for the masseter muscles was significantly higher in subjects with DS. The electrical potentials of the temporal and masseter muscles in children with DS were significantly lower compared to the corresponding parameters for healthy children when clenching.

Neonatal Hypotonia Following in Utero Exposure to Antidepressant Drugs.

Associations between fetal exposure to antidepressants and neonatal hypotonia were studied using VigiBase and the French PharmacoVigilance Database. We identified significant associations between neonatal hypotonia and clomipramine, venlafaxine, and imipramine. Reports from the French database implicated prolonged fetal exposure. Neonatal hypotonia may be associated with in utero exposure to antidepressants.

Estudo exploratório dos efeitos das terapias com eletroestimulação neuromuscular e dispositivos biomecânicos intraoral na saliva em pacientes com síndrome de Down e apneia obstrutiva do sono / Exploratory study of the effects of therapies with neuromuscular electrostimulation and intraoral biomechanical devices on saliva in patients with Down syndrome and obstructive sleep apnea

Este estudo tem como objetivo avaliar os efeitos das terapias com eletroestimulação neuromuscular e dispositivos biomecânicos intraorais sobre as propriedades físicoquímica e microbiológica da saliva em pacientes com síndrome de Down (SD) e apneia obstrutiva do sono (AOS). Ainda investigamos a morfologia das glândulas salivares maiores: parótidas, submandibulares e sublinguais para verificar possíveis desordens estruturais nesses indivíduos. Vinte e três pacientes adultos com SD e AOS, com idade entre 18 e 31 anos, de ambos os gêneros, foram convidados para participar deste estudo. Dentre esses pacientes, 18 concluíram as terapias propostas e foram divididos em três grupos: EENMs (n=7; terapia com eletroestimulação neuromuscular de superfície), DMHB (n=4; terapia com dispositivo mastigatório com hiperboloide) e AIOm (n=7; terapia com aparelho intraoral de avanço mandibular). A EENMs foi aplicada sobre os músculos masseter (porção superficial) e temporal (porção anterior), em ambos os lados. O DMHB foi posicionado entre as faces oclusais dos dentes posteriores e o paciente mordeu suas pontas ativas com hiperboloide. O AIOm foi utilizado somente no período de sono. Esse aparelho foi ativado lentamente, de 0,5 mm a 1,0 mm a cada 1 ou 2 semanas, respeitando as limitações fisiológicas do paciente. Todas as terapias foram realizadas durante 2 meses consecutivos. Antes e após as terapias propostas, testes de saliva foram realizados, incluindo taxa de fluxo salivar (TFS), valor de pH, capacidade tampão (CT), cortisol salivar matinal (CSmatinal) e noturno (CSnoturno) e identificação de Pseudomonas aeruginosas (P. aeruginosas). A seguir, a morfologia das glândulas salivares maiores, foram investigadas através do exame de ultrassonografia. Na análise estatística, teste de Wilcoxon (signed-rank test) para análise de correlação e teste de Kruskal-Wallis com o teste de Dunn para comparações múltiplas não paramétricas foram feitos. O nível de significância foi de p < 0,05. Embora a TFS tenha permanecido reduzida, a produção de saliva aumentou em todas as terapias. A TFS mostrou diferença estatística apenas no AIOm (p<0,0225). Houve diferença estatística no valor de pH apenas no EENMs (p < 0,0346). Nenhuma diferença estatística no CT foi encontrada; entretanto, os valores de normalidade foram alcançados (valores de limítrofe para normal) em 50% para DMHB e em 29% para EENMs e AIOm. Os valores normais de CSn não foram afetados, embora os níveis de CSn tenham aumentado estatisticamente na EENM (p < 0,0360) e entre as terapias EENM e AIOm (p < 0,0058). Nenhuma espécie de P. aeruginosa foi identificada em nossos pacientes antes das terapias. Neste estudo, pudemos concluir que a redução de fluxo salivar permaneceu nos pacientes com SD e AOS após as terapias propostas; entretanto, o AIOm seguido do DMHB mitigaram a severidade dessa alteração. A EENMs teve melhor desempenho em relação a qualidade da saliva quando comparado com as demais terapias. Dentre as terapias, os pacientes tratados com AIOm mostraram alta susceptibilidade ao estresse no período noturno. Nenhum paciente tinha risco de pneumonia por aspiração, antes das terapias. Nenhuma anomalia congênita de glândulas salivares maiores foi evidenciada, todavia alterações adquiridas foram observadas em alguns pacientes com SD e AOS (AU).

This study aims to evaluate the effects of neuromuscular electrostimulation therapies and intraoral biomechanical devices on the physicochemical and microbiological properties of saliva in patients with Down syndrome (DS) and obstructive sleep apnea (OSA). In addition, we investigated the major salivary glands' morphology: the glands of parotid, submandibular and sublingual to verify possible structural disorders in these individuals. Twenty-three adult patients with DS and OSA, with age range from 18 to 31 years old, of both genders, were invited to participate in this study. Among these patients, 18 patients completed the proposed therapies, and they were divided into three groups of therapy: sNME (n=7; therapy with surface neuromuscular electrostimulation), MDHB (n=4; therapy with masticatory device with hyperboloid) and mIOA (n= 7; therapy with mandibular advancement intraoral appliance). The sNME was applied on the masseter (superficial portion) and temporal (anterior portion) muscles on both the sides. The MDHB was positioned between the occlusal surfaces of the posterior teeth and the patient bit the active tips with hyperboloid. The mIOA was used only during the sleep. This appliance was activated slowly, from 0.5 mm to 1.0 mm per 1 to 2 weeks, respecting the patient's physiological limitations. All therapies were performed for 2 consecutive months. Before and after the proposed therapies, saliva tests were done, including salivary flow rate (SFR), pH value, buffering capacity (BC), morning (morningSC) and night (nightSC) salivary cortisol, and identification of Pseudomonas aeruginosa (P. aeruginosa). Furthermore, the major salivary glands' morphology, were investigated by means of ultrasound examination. For statistical analysis, Wilcoxon signed-rank test for correlation analysis and Kruskal-Wallis test with Dunn's test for nonparametric multiple comparisons were done. The level of significance was p < 0.05. Although SFR remained reduced, the saliva production increased in all therapies. The SFR showed a statistical difference only in the mIOA (p<0.0225). Despite the few variations in the pH value, there was a statistical difference only in the sNME (p<0.0346). No statistical difference was found in BC; however, the normality values were reached (borderline to normal values) in 50% for MDHB and in 29% for sNME and mIOA. The normal values of nSC were not affected, even though the nSC levels have increased statistically in NMES (p < 0.0360) and between the NMES and mIOA therapies (p <0.0058). No P. aeruginosa species was identified in our patients before the therapies. In this study, we concluded that the reduction in salivary flow remained in DS patients with DS and OSA after the proposed therapies; however, mIOA followed by MDHB mitigated the severity of this alteration. sNME showed better performance in relation to saliva quality when compared to other therapies. Among the therapies, patients treated with mIOA showed high susceptibility to stress, particularly at night. No patient had risk of aspiration pneumonia before the therapies. No congenital anomalies of major salivary glands were evidenced, but acquired alterations were observed in some patients with DS and OSA. (AU)

Acupuncture therapy combined with rhubarb applied to the umbilicus for constipation in patients with stage IV-V diabetic nephropathy / 中国基层医药

Objective:To investigate the efficacy of acupuncture therapy combined with rhubarb applied to the umbilicus in the treatment of constipation in patients with stage IV-V diabetic nephropathy.Methods:Ninety stage IV-V diabetic nephropathy patients with constipation, who received treatment in Wenzhou Hospital of Traditional Chinese Medicine from December 2019 to December 2020, were included in this study. They were randomly assigned to receive either routine treatment (control group, n = 45) or routine treatment plus acupuncture therapy combined with rhubarb applied to the umbilicus (study group, n = 45). Serum motilin, gastrin, and somatostatin levels and orocecal transit time pre- and post-treatment were compared between the two groups. The constipation severity was evaluated using the Constipation Severity Scale (CSS). Quality of life was evaluated using the Patient Assessment of Constipation Quality of Life Questionnaire. Clinical efficacy was compared between the two groups. Results:The somatostatin level and orocecal transit time post-treatment in the study group were (13.66 ± 4.24) ng/L and (80.58 ± 10.11) minutes, respectively, which were significantly lower than those in the control group [(19.31 ± 6.13) ng/L, (87.16 ± 12.04) minutes, t = 5.08, 2.80, both P < 0.05]. Serum motilin and gastrin levels post-treatment in the study group were (281.07 ± 41.16) ng/L and (181.07 ± 35.16) ng/L, respectively, which were significantly higher than those in the control group [(259.64 ± 39.83) ng/L, (162.65 ± 32.83) ng/L, t = 2.51, 2.56, both P < 0.05]. The scores of the Constipation Severity Scale and the Patient Assessment of Constipation Quality of Life Questionnaire post-treatment in the study group were (10.66 ± 3.14) points and (60.14 ± 13.64) points, respectively, which were significantly lower than those in the control group [ (15.31 ± 4.13) points, (71.61 ± 14.72) points, t = 6.01, 3.83, both P < 0.05). Total response rate was significantly higher in the study group than in the control group (97.78% vs. 80.00%, χ2 = 5.51, P < 0.05). Conclusion:Acupuncture therapy combined with rhubarb applied to the umbilicus can be used to treat constipation in patients with stage IV-V diabetic nephropathy. The combined therapy can adjust the secretion of gastrointestinal tract-related hormones, shorten orocecal transit time, improve clinical symptoms, and improve clinical efficacy and quality of life.

Clinical characteristics and genetic analysis of 23 newborns with hypotonia as the main manifestation / 中国新生儿科杂志

Objective:To study the role of neonatal panel detection based on next generation sequencing (NGS) combined with multiplex ligation-dependent probe amplification (MLPA) in the etiological differentiation of neonatal hypotonia.Methods:The clinical characteristics and gene test results of newborns with hypotonia as the main clinical manifestation treated at the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to March 2021 were retrospectively analyzed.Results:A total of 23 children with hypotonia and feeding difficulties diagnosed by gene tests were included. 17 cases (73.9%) had obvious abnormal appearance, and 11 cases (47.8%) had congenital heart disease (atrial septal defect and/or patent ductus arteriosus). Among the 23 infants, 21 were detected by panel gene, 10 by methylation specific MLPA (MS-MLPA) and 4 by MLPA (SMN1 / SMN2). 14 cases of Prader-Willi syndrome, 4 cases of spinal muscular atrophy, 3 cases of congenital myopathy and 2 cases of Schaaf-Yang syndrome were diagnosed. 11 cases died (47.8%), 9 cases had growth retardation (39.1%), 2 cases had normal growth and development (8.7%), and 1 case survived without detailed information (4.3%). Newborns with unknown etiology and low muscle tone are often complicated with abnormal appearance and congenital heart disease. Neonatal panel combined with MLPA is helpful for accurate diagnosis.Conclusions:The detection of neonatal panel combined with MLPA is cheap, and can provide accurate diagnosis for most newborns with unexplained hypotonia in a short diagnosis cycle, which is conducive to the early formulation of clinical decision-making, and guide the treatment, follow-up and genetic consultation of children.

Interrater Reliability among Novice Raters in the Assessment of Pelvic Floor Muscle Tone Using the Reissing Tone Scale.

Purpose: The authors sought to determine the interrater reliability among novice raters of intra-vaginal manual assessment of pubococcygeus muscle tone in women using the Reissing tone scale (RTS). Method: Three graduating physiotherapy students (novice raters) and one experienced pelvic floor physiotherapist assessed 31 female participants (aged 20-66 y). Assessors gave RTS scores for pubococcygeus tone at three intra-vaginal locations (6:00, 9:00, and 3:00). Interrater reliability was determined for the novice raters using a two-way random single-measures absolute agreement intra-class correlation coefficient (ICC). Spearman rank correlation (SRC) analysis determined the correlation between the novice and expert scores. Results: The ICC values for the novice raters were 0.523, 0.274, and 0.336 at 6:00, 9:00, and 3:00, and the SRC values between the novice and expert raters were 0.580, 0.320, and 0.340. Conclusions: The novice raters demonstrated low to moderate interrater reliability for intra-vaginal manual assessment of pubococcygeus tone. This result indicates that manual assessment of pelvic floor muscle tone is not reliable enough to use as a stand-alone test to guide treatment, at least for physiotherapists with limited clinical experience.

Objectif : déterminer la fiabilité interévaluateur des évaluateurs novices qui procèdent à l'évaluation intravaginale manuelle du tonus musculaire pubo-coccygien au moyen du score de tonus de Reissing (STR). Méthodologie : trois étudiants en physiothérapie finissants (les évaluateurs novices) et un physiothérapeute périnéal d'expérience ont évalué 31 participantes (âgées de 20 à 66 ans). Ils ont attribué un STR au tonus pubo-coccygien à trois foyers intravaginaux (à 6, 9 et 3 heures). Les chercheurs ont déterminé la fiabilité interévaluateur des évaluateurs novices au moyen d'un coefficient intraclasse de corrélation (CIC) à concordance absolue des mesures simples bidirectionnelles randomisées. Les chercheurs ont analysé la corrélation de Spearman (CdS) pour établir le lien entre les scores des novices et de l'expert. Résultats : la CIC des évaluateurs novices s'élevait à 0,523, 0,274 et 0,336 à 6, 9 et 3 heures, respectivement, et la CdS entre les évaluateurs novices et expert s'établissait à 0,580, 0,320 et 0,340. Conclusion : les évaluateurs novices ont démontré une fiabilité interévaluateur faible à modérée lors de l'évaluation intravaginale manuelle du tonus pubo-coccygien. Ainsi, l'évaluation manuelle du tonus périnéal n'est pas assez fiable si elle est utilisée seule pour orienter le traitement, du moins chez les physiothérapeutes ayant une expérience clinique limitée.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B / Aicardi-Goutières syndrome: a family case due to alteration of the RNASEH2B gene

Introducción: El síndrome de Aicardi-Goutières es una encefalopatía progresiva de inicio en el primer año de vida que condiciona retraso psicomotor, microcefalia y disfunción piramidal. Tiene una prevalencia de 1-5 de cada 10.000 recién nacidos vivos. La mayoría de los casos tiene transmisión autosómica recesiva, por alteración en siete genes implicados en el metabolismo del interferón, lo cual condiciona un aumento de sus niveles en la sangre y el líquido cefalorraquídeo, y afecta al cerebro (leucodistrofia, atrofia corticosubcortical, calcificaciones en los núcleos basales…), la piel y el sistema inmunitario. Caso clínico: Se trata de dos hermanos que presentan la variante p.Ala177Thr en homocigosis en el gen RNASEH2B; ambos progenitores, consanguíneos, son portadores. El primer hermano comenzó a los 10 meses con hipotonía axial, hipertonía de las extremidades, regresión psicomotriz y movimientos distónicos. El segundo hermano presentó desde el nacimiento tono axial bajo con hipertonía de las extremidades, a los 4 meses se hallaron calcificaciones en los núcleos lenticuloestriados mediante ecografía transfontalar y a los 6 meses inició movimientos distónicos y nistagmo intermitente. Ambos han desarrollado tetraparesia espástica y permanecen estables con 8 y 10 años, pese a las complicaciones propias del síndrome. Conclusiones: El síndrome de Aicardi-Goutières es una entidad rara que debe tenerse presente ante situaciones que cursen con alteración del desarrollo psicomotor y calcificaciones intracraneales; destacamos la importancia del diagnóstico genético tanto para conocer el pronóstico de nuestros pacientes en función de su alteración genética como para ofrecer consejo genético a sus familias.(AU)

Introduction: Aicardi-Goutières syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. Clinical case: They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. Conclusions: The Aicardi-Goutières syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.(AU)

Clinical characteristics of children affected by autism spectrum disorder with and without generalized hypotonia.

In this cross-sectional study, we aimed to evaluate the association between generalized hypotonia (GH) and demographic features and clinical characteristics in toddlers (2 to 5 years) with autism spectrum disorder (ASD). Among 93 children, 32 (34.4%) had GH. These patients had a later onset of independent walking (17 vs. 15 months, p < 0.01), a higher proportion of motor stereotypies (65.6 vs. 27.9%, p < 0.01), a lower mean total score in the parental-reported Generic Core Scale of Pediatric Quality of Life Inventory 4.0 (71 vs. 76 points, p 0.03), and a higher mean total score in the Calibrated Severity Score of Autism Diagnostic Observation Schedule version 2 at diagnosis (6 vs. 5 points, p 0.02) compared to the group without GH.Conclusion: Hypotonia is associated with other motor abnormalities and could be an early marker for higher autistic symptom severity and lower quality of life in young children with ASD. What is Known: • Motor function is closely related to autism spectrum disorder (ASD) • Muscle hypotonia is present in 15% to 67% of children with ASD What is New: • Muscle hypotonia is associated with higher autistic symptom severity and lower quality of life in children with ASD • Children with ASD and muscle hypotonia have more commonly motor stereotypies and a later onset of independent walking.

A mulher com hipotonia do assoalho pélvico: necessidades em cuidados de enfermagem / The woman with pelvic floor hypotonia: nursing care needs

A hipotonia do assoalho pélvico acarreta problemas do foro físico, psicossocial e económico na vida das mulheres. Entre as disfunções mais frequentes encontra-se a incontinência urinária e o prolapso dos órgãos pélvicos, que tem tido pouco investimento na área da reabilitação. Constituiu-se objetivo do estudo, compreender as necessidades em cuidados de enfermagem de reabilitação nas mulheres com hipotonia do assoalho pélvico, de modo a contribuir para uma melhor intervenção neste processo e suscitar nos profissionais de saúde a necessidade de desenvolvimento de competências nesta área. O estudo assenta numa abordagem qualitativa, exploratória e descritiva, com 10 mulheres com hipotonia do assoalho pélvico, selecionadas numa amostragem acidental. O procedimento de recolha de dados foi a entrevista semiestruturada, e para o tratamento dos dados, recorreu-se à análise de conteúdo. Dos dados emergiram cinco áreas temáticas. As disfunções do assoalho pélvico mais comuns foram as incontinências urinárias e o prolapso dos órgãos pélvicos. Estas disfunções têm implicações, nomeadamente nas atividades de vida; transtornos da imagem pessoal; alterações do sono, devido à sua interrupção frequente pela necessidade de urinar; a preocupação com a higiene íntima, devido aos odores e às perdas de urina; as alterações na atividade profissional; e a nível sexual, algumas mulheres referiram implicações e outras referiram não ter qualquer tipo de influência. No tratamento das disfunções emerge o cirúrgico, e o conservador, com referências ao uso de produtos absorventes, pessários, produtos farmacológicos e reforço dos músculos do assoalho pélvico. As atitudes das mulheres em relação às respostas dos serviços de saúde foram de aceitação das orientações/prescrições, da sua condição de saúde e expectativa ou não, quanto ao tratamento. A assistência de saúde foi essencialmente prestada pelos médicos, através de referenciação para especialistas, e quanto aos enfermeiros foi de mediação ou não existiu intervenção especifica. Em síntese, as implicações da hipotonia do assoalho pélvico têm no enfermeiro especialista em enfermagem de reabilitação, um vasto campo de intervenção aos diferentes níveis de prevenção, de forma a contribuir para uma melhor qualidade de vida das mulheres.

Pelvic floor hypotonic causes economic, physical, psychosocial problems in women's lives. There are several dysfunctions as a result from this problem, including incontinence and prolapse of the pelvic organs. It´s an issue that still has a weak investment in the area of rehabilitation. The aim of this study is to understand the needs in nursing care on women with pelvic floor muscle hypotonic, in order to contribute to an improved intervention in this process and to raise awareness in health professionals for the need to develop competencies in this area. The study is based on a qualitative, exploratory and descriptive approach. The data collection procedure was the semi-structured interview, directed to women with PFH. The analysis of the obtained data was performed through content analysis. Among the results, are highlighted the dysfunctions of the pelvic floor, like the Incontinence and the Prolapse of the pelvic floor. The implications in women's daily activities. Also relevant are the influence on women's self-esteem. In the sleep disorders, women also reported the need to urinate many times. Hygiene concerns, like the odors and losses of urine and all other constraints derived of this dysfunction on women's quality of life. Sexual life is also influenced by the pelvic floor disorders, like pain and fear to lose urine in the sexual act, but other women mentioned that this is not a problem to them. Other mentioned problem in their professional life. The usual offered treatment pharmacological, use of absorbent dressings, pessaries, strengthening of pelvic muscles and surgery. The treatment of choice is surgery, mainly due to lack of professional knowledge or sensitivity to refer these cases for rehabilitation. The attitudes of these women in relation to the responses of the health services were acceptance of the guidelines or prescriptions, their health condition and expectations or not regarding the treatment. Generally, women with Pelvic Floor Hypotonia are referred for treatment by family doctors, who lead them to urogynecologist's. The specialist nurse in rehabilitation nursing area develops its work in the processes of prevention and rehabilitation. Scientific evidence demonstrates that pelvic hypotonia has negative impact on women's quality of life. This way, the interaction of a Nurse in rehabilitation in the multidisciplinary women's health teams is important.

Classification of Congenital Zika Syndrome: Muscle Tone, Motor Type, Body Segments Affected, and Gross Motor Function.

Aim: To identify abnormalities in muscle tone and motor function associated with congenital Zika syndrome (CZS).Method: A cross-sectional observational study involving 96 children (55 males) with CZS at a mean (SD) age 35.2 ± 2.9 months. Children's muscle tone was investigated using the pull to sit, scarf sign, shoulder suspension and ventral suspension tests and the modified Ashworth scale (MAS). Motor impairment was determined using the Gross Motor Function Classification System (GMFCS) and body segments most affected with motor impairment.Results: 58 (60,5%) children tested positive for ≥1 maneuver used to evaluate muscle tone, while 38 (39.5%) tested negative in all the tests. MAS score was >0 for at least one of the appendicular muscles in 91 children (94.8%). In 88 children (91.7%), all four limbs were affected.Conclusion: Findings suggestive of axial hypotonia and appendicular hypertonia associated with severe motor impairment were prevalent in children with CZS.

Early onset neutral lipid storage disease with myopathy presenting as congenital hypotonia and hepatomegaly.

Neutral lipid storage disease with myopathy is an ultra-rare, inherited autosomal recessive neuromuscular metabolic disorder caused by pathogenic variants in PNPLA2. It typically presents in adults as a progressive myopathy and is associated with myocardiopathy, hepatic involvement, and high creatine kinase levels. Only three children and adolescents with neutral lipid storage disease with myopathy have been reported. We report a female infant with congenital hypotonia born to consanguineous parents, whose mother presented with polyhydramnios during pregnancy. She demonstrated delayed acquisition of motor milestones, hepatomegaly, and elevated creatine kinase levels. Homozygous pathogenic variants in PNPLA2 were identified. Lipid accumulation was observed within the muscle fibers and Jordans' anomaly was observed in a blood smear. This is the first report to describe an infant with mildly symptomatic neutral lipid storage disease with myopathy and demonstrate hepatic involvement in a pediatric patient. Despite her mild symptoms, her ancillary test results were markedly abnormal.

Schaaf-Yang syndrome in a neonate caused by MAGEL2 gene mutation: a case report / 中华围产医学杂志

In this study, we reported a patient with neonatal-onset Schaaf-Yang syndrome (SYS). The girl was the second singleton child of a healthy, nonconsanguineous couple. She suffered from hypoxic asphyxia at birth and soon developed persistent respiratory distress. She was also diagnosed with neonatal encephalopathy, congenital heart disease, pneumonia, sepsis, neonatal jaundice, congenital laryngeal achondroplasia, and paralysis of vocal cord were diagnosed after admission. She spent the first one month of life in the neonatal intensive care unit and was treated with mechanical ventilation, nutritional support and anti-infectives. Then the baby was discharged as her parents' request and died of respiratory failure at the age of 2 months. Whole exome sequencing detected, a heterozygous nonsense mutation of c.1912C>T(p.Q638X) in MAGEL2 in the fetus, which was inherited from her father but not found in her mother.