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LAMA2-related muscular dystrophy is caused by pathogenic variants of the alpha2 subunit of Laminin. This common form of muscular dystrophy is characterized by elevated CK >1000IU/L, dystrophic changes on muscle biopsy, complete or partial absence of merosin staining, and both central and peripheral nervous system involvement. Advancements in genomic testing using NGS and wider application of RNA sequencing has expanded our knowledge of novel non-coding pathogenic variants in LAMA2. RNA sequencing is an increasingly utilized technique to directly analyze the transcriptome, through creation of a complementary DNA (cDNA) from the transcript within a tissue sample. Here we describe a homozygous deep intronic variant that produces a novel splice junction in LAMA2 identified by RNA sequencing analysis in a patient with a clinical phenotype in keeping with LAMA2-related muscular dystrophy. Furthermore, in this case merosin staining was retained suggestive of a functional deficit.
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Íntrons , Laminina , Distrofias Musculares , Análise de Sequência de RNA , Humanos , Laminina/genética , Íntrons/genética , Distrofias Musculares/genética , Distrofias Musculares/patologia , Distrofias Musculares/diagnóstico , Masculino , Fenótipo , Mutação , FemininoRESUMO
LAMB2 gene disorders present with different phenotypes. Pierson syndrome (PS) is a common phenotype associated with LAMB2 variants. Neuromuscular phenotype has been reported including hypotonia and developmental delay. However, neuromuscular junction abnormalities represented as congenital myasthenic syndrome (CMS) was reported in one adult patient only. Here, in this paper, we present two pediatric cases with a severe presentation of PS and have CMS so expanding the knowledge of LAMB2 related phenotypes. The first patient had hypotonia and global developmental delay. Targeted genetic testing panel demonstrated homozygous pathogenic variant in the LAMB2 gene (c.5182C>T, pGln1728*) which was reported by Maselli et al. 2009. Repetitive nerve stimulation (RNS) showed a decremental response at low frequency of 3 Hz. On the other hand, the second patient had profound weakness since birth. Tri-Whole exome sequencing showed homozygous pathogenic variant in the LAMB2 gene c.2890C>T, pArg964*. A trial of salbutamol did not improve the symptoms. Both patients passed away from sequala of PS. The spectrum of phenotypic changes associated with LAMB2 mutations is still expanding, and further investigation into the various clinical and morphologic presentations associated with these mutations is important to better identify and manage affected individuals.
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Síndromes Miastênicas Congênitas , Humanos , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/fisiopatologia , Síndromes Miastênicas Congênitas/diagnóstico , Masculino , Feminino , Anormalidades do Olho/genética , Anormalidades do Olho/complicações , Laminina/genética , Fenótipo , Mutação , Anormalidades Múltiplas/genética , Lactente , Doenças da Junção Neuromuscular/genética , Pré-Escolar , Síndrome Nefrótica , Distúrbios PupilaresRESUMO
Status dystonicus is the most severe form of dystonia with life-threatening complications if not treated promptly. We present consensus recommendations for the initial management of acutely worsening dystonia (including pre-status dystonicus and status dystonicus), as well as refractory status dystonicus in children. This guideline provides a stepwise approach to assessment, triage, interdisciplinary treatment, and monitoring of status dystonicus. The clinical pathways aim to: (1) facilitate timely recognition/triage of worsening dystonia, (2) standardize supportive and dystonia-directed therapies, (3) provide structure for interdisciplinary cooperation, (4) integrate advances in genomics and neuromodulation, (5) enable multicenter quality improvement and research, and (6) improve outcomes. © 2024 International Parkinson and Movement Disorder Society.
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PURPOSE: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases. METHODS: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests. RESULTS: Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses. CONCLUSION: We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test.
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Exoma , Doenças Raras , Humanos , Estudos Prospectivos , Sequenciamento do Exoma , Doenças Raras/diagnóstico , Doenças Raras/genética , Testes Genéticos/métodos , OntárioRESUMO
Spinal muscular atrophy (SMA) is a neuromuscular genetic disorder caused by the loss of lower motor neurons leading to progressive muscle weakness and atrophy. With the rise of novel therapies and early diagnosis on newborn screening (NBS), the natural history of SMA has been evolving. Earlier therapeutic interventions can modify disease outcomes and improve survival. The role of treatment in infants born preterm is an important question given the importance of early intervention. In this study, we discuss the case of an infant born at 32 weeks who was diagnosed with SMA on NBS and was treated with Spinraza® (Nusinersen) and Zolgensma® (Onasemnogene abeparvovec-xioi) within the first 2 months of life. With the scarce evidence that currently exists, clinicians should be aware of the efficacy and safety impact of early therapy particularly in the preterm infant.
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BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disorder that may result in neuromuscular weakness and respiratory insufficiency. Gene replacement therapy has changed the trajectory of this condition, but long-term outcomes related to sleep disordered breathing are not known. METHODS: This was a retrospective review of infants with SMA identified via newborn screening who subsequently received onasemnogene abeparvovec at the Hospital for Sick Children (Ontario, Canada). Polysomnograms were conducted at the time of confirmed diagnosis as well as regularly thereafter. RESULTS: Eleven children (4 female) were identified via newborn screen (7 with 2 copies of the SMN2 gene and 4 with 3 copies of the SMN2 gene) and received onasemnogene abeparvovec at a median age of 3.6 weeks. All eleven infants met criteria for sleep disordered breathing based on their first completed polysomnograms but improved over time. Three infants required respiratory technology, including a premature infant who was prescribed nocturnal supplemental oxygen therapy for central sleep apnea and two symptomatic infants with neuromuscular weakness who required nocturnal noninvasive ventilation. We did not find a correlation between motor scores and polysomnogram parameters. CONCLUSION: Children treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time. Polysomnograms revealed abnormal parameters in all children, but the clinical significance of these findings was unclear for children who were asymptomatic for sleep disordered breathing or neuromuscular weakness. These results highlight the need to evaluate both motor scores and respiratory symptoms to ensure a holistic evaluation of clinical status.
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Atrofia Muscular Espinal , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Atrofias Musculares Espinais da Infância , Criança , Recém-Nascido , Humanos , Lactente , Feminino , Triagem Neonatal , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/terapia , Ontário , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/terapiaRESUMO
Titin-related myopathy is an emerging genetic neuromuscular disorder with a wide spectrum of clinical phenotypes. To date, there have not been reports of patients with this disease that presented with extraocular muscle involvement. Here we discuss a 19-year-old male with congenital weakness, complete ophthalmoplegia, thoracolumbar scoliosis, and obstructive sleep apnea. Muscle magnetic resonance imaging revealed severe involvement of the gluteal and anterior compartment muscles, and clear adductor sparing, while muscle biopsy of the right vastus lateralis showed distinctive cap-like structures. Trio Whole Exome Sequencing (WES) showed compound heterozygous likely pathologic variants in the TTN gene. (c.82541_82544dup (p.Arg27515Serfs*2) in exon 327 (NM_001267550.2) and c.31846+1G>A (p.?) in exon 123 (NM_001267550.2). To our knowledge, this is the first report of a TTN-related disorder associated with ophthalmoplegia.
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Doenças Musculares , Doenças Neuromusculares , Oftalmoplegia , Humanos , Masculino , Adulto Jovem , Conectina/genética , Músculo Esquelético/patologia , Doenças Musculares/genética , Doenças Musculares/patologia , Mutação , Doenças Neuromusculares/patologia , Oftalmoplegia/genética , Oftalmoplegia/patologia , FenótipoRESUMO
Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7, TPM1, and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genes such as MYH2, TPM2, and TNNI2 that encode parts of the skeletal muscle sarcomere cause muscle diseases affecting skeletal muscle, such as distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g., MYH7) encoding sarcomeric proteins in which the same pathogenic variant affects skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain pathogenic variants that also cause cardiac abnormalities. We report five families with DA because of heterozygous missense variants in the gene actin, alpha, cardiac muscle 1 (ACTC1). ACTC1 encodes a highly conserved actin that binds to myosin in cardiac and skeletal muscle. Pathogenic variants in ACTC1 have been found previously to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition because of variants in ACTC1 and suggests that some functions of ACTC1 are shared in cardiac and skeletal muscle.
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Artrogripose , Cardiomiopatias , Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Cardiopatias Congênitas , Doenças Musculares , Humanos , Artrogripose/genética , Actinas/genética , Cardiopatias Congênitas/complicações , Cardiomiopatias/etiologia , Cardiomiopatia Dilatada/complicações , Doenças Musculares/complicações , Miosinas , Cardiomiopatia Hipertrófica/complicaçõesRESUMO
OBJECTIVE: Spinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers' experiences with disease-modifying therapies for SMA. DESIGN: Qualitative study including semistructured interviews with caregivers of children with SMA who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, coded and analysed using content analysis. SETTING: The Hospital for Sick Children (Toronto, Canada). RESULTS: Fifteen family caregivers of children with SMA type 1 (n=5), type 2 (n=5) and type 3 (n=5) participated. There were two emerging themes and several subthemes (in parentheses): (1) inequities in access to disease-modifying therapies (variable regulatory approvals, prohibitively expensive therapies and insufficient infrastructure) and (2) patient and family experience with disease-modifying therapies (decision making, hope, fear and uncertainty). CONCLUSION: The caregiver experience with SMA has been transformed by the advent of disease-modifying therapies. Consistent and predictable access to disease-modifying therapies is a major concern for caregivers of children with SMA but is influenced by regulatory approvals, funding and eligibility criteria that are heterogenous across jurisdictions. Many caregivers described going to great lengths to access therapies, highlighting issues related to justice, such as equity and access. This diverse population reflects contemporary patients and families with SMA; their broad experiences may inform the healthcare delivery of other emerging orphan drugs.
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Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Criança , Humanos , Cuidadores , Atrofia Muscular Espinal/tratamento farmacológico , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Pesquisa Qualitativa , IncertezaRESUMO
Limb girdle muscle dystrophies (LGMDs) are a group of inherited neuromuscular disorders comprising more than 20 genes. There have been increasing efforts to characterize this group with Muscle MRI. However, due to the complexity and similarities, the interpretation of the MRI patterns is usually done by experts in the field. Here, we proposed a step-by-step image interpretation of Muscle MRI in LGDM by evaluating the variability of muscle pattern involvement reported in the literature. A systematic review with an open start date to November 2022 was conducted to describe all LGMDs' muscle MRI patterns. Eighty-eight studies were included in the final review. Data were found to describe muscle MRI patterns for 15 out of 17 LGMDs types. Although the diagnosis of LGMDs is challenging despite the advanced genetic testing and other diagnostic modalities, muscle MRI is shown to help in the diagnosis of LGMDs. To further increase the yield for muscle MRI in the neuromuscular field, larger cohorts of patients need to be conducted.
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Distrofia Muscular do Cíngulo dos Membros , Doenças Neuromusculares , Humanos , Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular do Cíngulo dos Membros/diagnóstico por imagem , Distrofia Muscular do Cíngulo dos Membros/genética , Doenças Neuromusculares/genética , Imageamento por Ressonância Magnética , Testes GenéticosRESUMO
Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7 , TPM1 , and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genes MYH2 , TPM2 , and TNNI2 , that encode parts of the skeletal muscle sarcomere, cause muscle diseases affecting skeletal muscle, such as the distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g., MYH7 ) encoding sarcomeric proteins in which the same pathogenic variant affects both skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain mutations that also cause cardiac abnormalities. We report five families with DA due to heterozygous missense variants in the gene actin, alpha, cardiac muscle 1 ( ACTC1 ). ACTC1 encodes a highly conserved actin that binds to myosin in both cardiac and skeletal muscle. Mutations in ACTC1 have previously been found to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition due to mutations in ACTC1 and suggests that some functions of actin, alpha, cardiac muscle 1 are shared in cardiac and skeletal muscle.
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Phosphoenolpyruvate carboxykinase (PCK) plays a critical role in cytosolic gluconeogenesis, and defects in PCK1 cause a fasting-aggravated metabolic disease with hypoglycemia and lactic acidosis. However, there are two genes encoding PCK, and the role of the mitochondrial resident PCK (encoded by PCK2) is unclear, since gluconeogenesis is cytosolic. We identified three patients in two families with biallelic variants in PCK2. One has compound heterozygous variants (p.Ser23Ter/p.Pro170Leu), and the other two (siblings) have homozygous p.Arg193Ter variation. All three patients have weakness and abnormal gait, an absence of PCK2 protein, and profound reduction in PCK2 activity in fibroblasts, but no obvious metabolic phenotype. Nerve conduction studies showed reduced conduction velocities with temporal dispersion and conduction block compatible with a demyelinating peripheral neuropathy. To validate the association between PCK2 variants and clinical disease, we generated a mouse knockout model of PCK2 deficiency. The animals present abnormal nerve conduction studies and peripheral nerve pathology, corroborating the human phenotype. In total, we conclude that biallelic variants in PCK2 cause a neurogenetic disorder featuring abnormal gait and peripheral neuropathy.
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Doenças do Sistema Nervoso Periférico , Fosfoenolpiruvato Carboxiquinase (ATP) , Camundongos , Animais , Humanos , Fosfoenolpiruvato , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Gluconeogênese/genética , Fosfoenolpiruvato Carboxilase/metabolismo , Doenças do Sistema Nervoso Periférico/genéticaRESUMO
BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a neuromuscular disorder with a natural history of chronic respiratory failure and death during infancy without ventilation. Recently, disease-modifying therapies such as nusinersen have improved disease trajectory. However, objective data on the trajectory of polysomnography outcomes, the relationship between motor scores and respiratory parameters, respiratory technology dependence and healthcare utilization in children with SMA1 remain to be elucidated. METHODS: This was a retrospective observational study of children with SMA1 receiving nusinersen between October 2016 and February 2021 at two tertiary care hospitals in Canada. Baseline polysomnography data, motor scores, respiratory technology, and unanticipated healthcare utilization were examined. RESULTS: Eleven children (five females, two SMN2 copies each) were included. Median (interquartile range [IQR]) age at diagnosis was 3.6 (2.8-5.0) months and age at diagnostic polysomnogram following nusinersen initiation was 9.4 (5.3-14.0) months. Nusinersen was initiated at a median (IQR) age of 5.4 (3.4-7.6) months and 8/11 children had respiratory symptoms at that time. Diagnostic polysomnography data showed a median (IQR) central apnea-hypopnea index (AHI) of 4.1 (1.8-10.0) and obstructive AHI of 2.2 (0-8.0) events/h. We observed an inverse relationship between motor scores and central apnea-hypopnea indices. All children required ventilatory support at the end of the study period. CONCLUSION: This study showed abnormal polysomnography parameters and need for ventilation despite nusinersen suggesting ongoing need for regular monitoring with polysomnography. Understanding the respiratory disease trajectory of children undergoing treatment with nusinersen will inform decision-making regarding optimal timing of ventilatory support initiation.
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Atrofia Muscular Espinal , Apneia do Sono Tipo Central , Atrofias Musculares Espinais da Infância , Feminino , Criança , Humanos , Lactente , Atrofias Musculares Espinais da Infância/complicações , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , RespiraçãoRESUMO
OBJECTIVES: We aimed to explore the prevalence of peroneal neuropathy in children during coronavirus disease-19 (COVID-19) pandemic. BACKGROUND: Since the COVID-19 outbreak, many children worldwide have experienced a dramatic lifestyle changes, including conducting most daily activities indoors. Peroneal nerve palsy is one of the most common entrapment neuropathies and circumstances as prolonged immobilization or leg crossing predisposes an individual to peroneal neuropathy. METHODS: This is a case-control retrospective study that included patients referred to our neurophysiology clinic with foot drop. We compared the prevalence of spontaneous peroneal neuropathy 1 year before (April 2019/March 2020) and 1 year during the COVID-19 pandemic (April 2020/March 2021); and we also continued collecting data prospectively between April and September 2021 analysis the whole pandemic period. RESULTS: Totally, 399 patient clinical notes and NCS/EMG reports were reviewed, 220 were evaluated 1 year before and 179 1 year during COVID-19 pandemic. During the COVID-19 pandemic, there was a higher prevalence of peroneal neuropathy (odds ratio 4.74, 95%CI 1.30-17.25, p = 0.0183). In the COVID group (n = 11), mean age was 14 years and 63.4% were males. Mean age was 15 years and 66.7% were males in the Control group (n = 3). There was a significant difference in the time from symptoms onset to the neurophysiology assessment, with a mean time of 14 days in the Control group and 87.5 days in the COVID group. CONCLUSIONS: This study provides evidence that during the COVID-19 pandemic period, there was a higher prevalence of peroneal neuropathy among children. Strategies to prevent peroneal neuropathy should be recommened to this age group.
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COVID-19 , Neuropatias Fibulares , Masculino , Humanos , Criança , Adolescente , Feminino , Neuropatias Fibulares/epidemiologia , Neuropatias Fibulares/diagnóstico , Pandemias , Estudos Retrospectivos , Prevalência , COVID-19/epidemiologiaRESUMO
Background and Objectives: The introduction of spinal muscular dystrophy (SMA)-modifying therapies, such as antisense oligonucleotide therapy, has changed the natural history of SMA. Most reports on treatment outcomes have focused on motor scores and respiratory function. The objective of this study is to document the development and progression of scoliosis in patients with SMA1 treated with nusinersen. Methods: A descriptive single-center study was conducted in patients with SMA1 who were treated with nusinersen before 6 months of age. Data were collected on patients who met criteria, including age at the first nusinersen dose, number of nusinersen doses, degree of scoliosis, respiratory parameters, feeding route, and motor scores at baseline and follow-up. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was subanalyzed using axial (AxS) and appendicular motor (ApS) scores to evaluate a possible correlation between scoliosis and axial muscle strength. Results: From our cohort, 31 percent (11/35) of patients had a diagnosis of SMA1. Sixty-three percent (7/11) met the inclusion criteria. All patients (7/7) showed initial improvement in their CHOP-INTEND scores in correlation with improvement on the ApS. Despite this, most patients did not show improvement in the AxS. Subsequently, all patients developed scoliosis in the first year of life with Cobb angles that ranged between 18° and 60°. Furthermore, total CHOP-INTEND scores had dropped in 2 patients alongside the development of a Cobb angle of >40°. Discussion: Despite the significant improvement in functional motor assessment in patients with SMA1, there is a progression of significant scoliosis despite treatment. Subsequently, lack or minimal improvement on the axial CHOP-INTEND scores may predict worsening on the total motor scores.
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PURA syndrome is caused by heterozygous de novo pathogenic variants in PURA. It is characterized by moderate to severe neurodevelopmental disability with a wide clinical spectrum and an evolving phenotype. We present two individuals with genetically confirmed PURA syndrome who had severe neonatal signs and symptoms and a novel phenotype suggestive of neuromuscular junction pathology. We demonstrate that PURA syndrome shares features consistent with a congenital myasthenic syndrome; we thus recommend electrodiagnostic study in neonates and infants with PURA syndrome, and consideration of salbutamol as a therapeutic option.
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Epilepsia , Deficiência Intelectual , Síndromes Miastênicas Congênitas , Humanos , Deficiência Intelectual/genética , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Junção Neuromuscular , Fenótipo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genéticaRESUMO
X-linked myotubular myopathy (XLMTM) is a severe monogenetic disorder of the skeletal muscle. It is caused by loss-of-expression/function mutations in the myotubularin (MTM1) gene. Much of what is known about the disease, as well as the treatment strategies, has been uncovered through experimentation in pre-clinical models, particularly the Mtm1 gene knockout mouse line (Mtm1 KO). Despite this understanding, and the identification of potential therapies, much remains to be understood about XLMTM disease pathomechanisms, and about the normal functions of MTM1 in muscle development. To lay the groundwork for addressing these knowledge gaps, we performed a natural history study of Mtm1 KO mice. This included longitudinal comparative analyses of motor phenotype, transcriptome and proteome profiles, muscle structure and targeted molecular pathways. We identified age-associated changes in gene expression, mitochondrial function, myofiber size and key molecular markers, including DNM2. Importantly, some molecular and histopathologic changes preceded overt phenotypic changes, while others, such as triad structural alternations, occurred coincidentally with the presence of severe weakness. In total, this study provides a comprehensive longitudinal evaluation of the murine XLMTM disease process, and thus provides a critical framework for future investigations.
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Miopatias Congênitas Estruturais , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , FenótipoRESUMO
Transition in paediatric health care refers to the planned process of shifting to an adult model of care and is highly individualised, patient focussed and requires a coordinated effort from different health care professionals. Through this retrospective study, we describe the spectrum of neuromuscular diseases evaluated through a paediatric to adult neuromuscular transition program in a tertiary academic centre in Canada, and also the speciality supports needed for these patients. 126 patients were transitioned during the study period. The most common clinical diagnosis was muscle disease (44.4%), followed by neuropathy (27.8%), neuromuscular junction disorders (15.9%) and motor neuron disease (MND) (10.3%). The majority of cases were inherited neuromuscular disorders (66.6%); 58.3% had a genetically confirmed diagnosis. Cardiac and respiratory abnormalities were encountered in 8.7% and 27.7% and transitioning was required for 39.8% and 35.7% respectively. Scoliosis was seen in 30.2% of patients; 9.5% underwent spine surgery. Patients with MND had maximum requirements for self-care (46.2% of MND) and a mobility device for ambulation was required in 69.2% of MND. We observed a wide range of systemic issues requiring the services of endocrinology, gastroenterology, speech and language pathology and psychiatry. A multidisciplinary clinical care model may provide optimal care for patients transitioning from paediatric to adult care health systems.