RESUMO
A 21-year-old woman developed an acute myotonic reaction while undergoing anaesthesia using succinylcholine. Examination later showed she had shoulder, neck and calf hypertrophy, bilateral symmetrical ptosis and eyelid, handgrip and percussion myotonia. Peripheral neurophysiology studies identified significant, continuous myotonic discharges in both upper and lower limbs. Genetic analysis identified a c.3917G>A (p.Gly1306Glu) mutation in the SCN4A gene, confirming a diagnosis of sodium channel myotonia. Succinylcholine and other depolarising agents can precipitate life-threatening acute myotonic reactions when given to patients with myotonia. Patients with neuromuscular disorders are at an increased risk of perioperative anaesthetic complications. We report a woman who developed an acute myotonic reaction whilst undergoing anaesthesia, in the context of an unrecognised myotonic disorder. We then discuss an approach to the diagnosis of myotonic disorders.
Assuntos
Anestesia , Miotonia , Transtornos Miotônicos , Feminino , Humanos , Adulto Jovem , Adulto , Succinilcolina/efeitos adversos , Força da Mão , Transtornos Miotônicos/induzido quimicamente , Transtornos Miotônicos/diagnóstico , Miotonia/induzido quimicamente , Miotonia/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genéticaRESUMO
Non-dystrophic myotonias are a group of rare neuromuscular diseases linked to SCN4A or CLCN1. Among the subtypes, myotonia permanens, associated with the Gly1306Glu variant of SCN4A, is a relatively less frequent but more severe form. Most reports of non-dystrophic myotonias describe European populations. Therefore, to expand the genetic and phenotypic spectrum of this disorder, we evaluated 30 Chilean patients with non-dystrophic myotonias for associated variants and clinical characteristics. SCN4A variants were observed in 28 (93%) of patients, including 25 (83%) with myotonia permanens due to the Gly1306Glu variant. Myotonia permanens was inherited in 24 (96%) patients; the mean age of onset was 6 months, and the initial symptoms were orbicularis oculi myotonia in 17 (74%) patients and larynx myotonia in 12 (52%) patients. The extraocular muscles were involved in 11 (44%) patients, upper limbs in 20 (80%), and lower limbs in 21 (84%). Thirteen (52%) patients experienced recurrent pain and 10 (40%) patients reported limitations in daily life activities. Carbamazepine reduced myotonia in eight treated patients. The high frequency of the Gly1306Glu variant in SCN4A in Chilean patients suggests a founder effect and expands its phenotypic spectrum.
Assuntos
Miotonia/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Adolescente , Adulto , Criança , Chile , Estudos de Coortes , Feminino , Efeito Fundador , Humanos , Lactente , Masculino , Mutação , Transtornos Miotônicos/genética , Adulto JovemRESUMO
OBJECTIVE: To ascertain the presenting symptoms of children with skeletal muscle channelopathies to promote early diagnosis and treatment. STUDY DESIGN: Retrospective case review of 38 children with a skeletal muscle channelopathy attending the specialist pediatric neuromuscular service at Great Ormond Street Hospital over a 15-year period. RESULTS: Gait disorder and leg cramps are a frequent presentation of myotonic disorders (19 of 29). Strabismus or extraocular myotonia (9 of 19) and respiratory and/or bulbar symptoms (11 of 19) are common among those with sodium channelopathy. Neonatal hypotonia was observed in periodic paralysis. Scoliosis and/or contractures were demonstrated in 6 of 38 children. School attendance or ability to engage fully in all activities was often limited (25 of 38). CONCLUSIONS: Children with skeletal muscle channelopathies frequently display symptoms that are uncommon in adult disease. Any child presenting with abnormal gait, leg cramps, or strabismus, especially if intermittent, should prompt examination for myotonia. Those with sodium channel disease should be monitored for respiratory or bulbar complications. Neonatal hypotonia can herald periodic paralysis. Early diagnosis is essential for children to reach their full educational potential.
Assuntos
Canalopatias/complicações , Transtornos Miotônicos/diagnóstico , Canais de Sódio/genética , Absenteísmo , Adolescente , Obstrução das Vias Respiratórias , Canalopatias/diagnóstico , Criança , Pré-Escolar , Contratura/etiologia , Diplopia/etiologia , Feminino , Transtornos Neurológicos da Marcha , Humanos , Lactente , Recém-Nascido , Masculino , Cãibra Muscular/etiologia , Hipotonia Muscular/etiologia , Transtornos Miotônicos/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Sons Respiratórios/etiologia , Estudos Retrospectivos , Escoliose/etiologia , Estrabismo/etiologiaRESUMO
Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases. In these seemingly unrelated biological processes, CNBP appears to be involved in controlling cell death and proliferation rates. Low levels of CNBP may reduce rate of global protein synthesis, thereby reducing proliferation and increasing apoptosis. Conversely, CNBP might affect transcription of genes required for cell proliferation. Experimental evidences gathered so far make it difficult to ascertain or rule out any of these possibilities. Moreover, both possibilities may not be mutually exclusive. CNBP is a small and strikingly conserved single-stranded nucleic acid binding protein that is able to bind DNA as well as RNA. CNBP has a broad spectrum of targets, ranging from regulatory sites in gene promoters to translational regulatory elements in mRNA untranslated regions. Biochemical experiments have recently shed light on the possible mechanism of action for CNBP, which may act as a nucleic acid chaperone catalyzing the rearrangement of G-rich nucleic acid secondary structures likely relevant for transcriptional and/or translational gene regulation. This review focuses on the involvement of CNBP in vertebrate craniofacial development and human DM2 and sIBM diseases, as well as on the biochemical and structural features of CNBP and its cellular and molecular mechanism of action.
Assuntos
Morte Celular , Proteínas de Ligação a RNA/genética , Animais , Morte Celular/genética , Proliferação de Células , Anormalidades Craniofaciais/etiologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Camundongos Knockout , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Miosite de Corpos de Inclusão/etiologia , Transtornos Miotônicos/etiologia , Distrofia Miotônica , Homologia de Sequência do Ácido Nucleico , Xenopus laevisRESUMO
La frecuencia del quiste epidermoide es baja, su transformación maligna lo es aún más. Se presenta el caso de un quiste epidermoide parcialmente resecado que ocho años mas tarde cursó como carcinoma escamocelular
Assuntos
Humanos , Miotonia , Cisto Epidérmico , Transtornos Miotônicos , ColômbiaRESUMO
En éste artículo se describen los diferentes tipos del miotonía, entidades relacionadas, fisiopatología y manejo, haciendo énfasis en la paramiotonía congénita
Assuntos
Humanos , Miotonia , Transtornos Miotônicos , Miotonia CongênitaRESUMO
AIM: The aim is to review the molecular and genetic aspects of the dystrophic and no dystrophic myotonias. BACKGROUND: Myotonic diseases are hereditary conditions of the skeletal muscle, classified in two groups depending on the symptoms. In the first group are the myotonic dystrophies, with the myotonic dystrophies type 1 and 2. In the second group are the channelopathies, characterized for the affected function of the ion channels. Myotonic dystrophy type 1, a neurodegenerative, progressive and disabling disease is caused by an expansion of the CTG trinucleotide, its size shows a positive correlation with the severity and negative with age of onset. There are enough insights to think that the gain of function of the mutant ARN is the pathophysiological mechanism occurring on this disease. Myotonic dystrophy type 2, less severe than type 1, is caused by an expansion of the CCTG tetranucleotide, its pathophysiological mechanism is similar to that one proposed for the type 1. In the second group we can find the chloride channelopathies, with autosomal dominant or recessive inheritance, caused by one of the 60 different mutations on the chloride channel gene; and the sodium channelopathies, group of three clinically overlapping diseases, with dominant heredity caused by one of the 25 different mutations on the sodium channel gene. CONCLUSIONS: These diseases are highly clinically variable, and even though their genetic base is known, it is necessary too much research in order to understand their pathophisiology and the phenotype genotype relationships.
Assuntos
Transtornos Miotônicos/genética , Regiões 3' não Traduzidas/genética , Idade de Início , Canais de Cloreto/deficiência , Canais de Cloreto/genética , Cromossomos Humanos Par 19/genética , Frequência do Gene , Humanos , Canais Iônicos/deficiência , Canais Iônicos/genética , Canais Iônicos/fisiologia , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Proteínas Musculares/fisiologia , Transtornos Miotônicos/classificação , Transtornos Miotônicos/epidemiologia , Distrofia Miotônica/classificação , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/genética , Miotonina Proteína Quinase , Canal de Sódio Disparado por Voltagem NAV1.4 , Paralisia Periódica Hiperpotassêmica/genética , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Proteínas de Ligação a RNA/genética , Canais de Sódio/deficiência , Canais de Sódio/genética , Expansão das Repetições de TrinucleotídeosRESUMO
INTRODUCTION: The ionic channels are complex glycoprotein structures, which cross the lipidic cellular membrane and allow the passage of electrically charged ions from one side of it to the other, thanks to the electrochemical gradient. A channelopathy is a disorder due to anomalous function of the ionic channels. DEVELOPMENT: In this study we analyze particularly the hereditary channelopathies with neuromuscular involvement non dystrophic myotonia, paramyotonias and periodic paralysis, and classify the clinical, physiopathological, molecular, genetic and therapeutic aspects. As far as possible we have divided the different conditions according to the channel involved, due to mutations which affect the sodium, calcium, chloride and potassium channels. We have also included neuromyotonic phenomena which are probably caused by channelopathies. CONCLUSIONS: Probably it will not be long before many of the conditions considered in this article have a better physiopathological explanation, more specific diagnostic procedures and a more rational approach to treatment.