RESUMO
Few reliable data exist on the prevalence of skeletal muscle channelopathies. We determined the minimum point prevalence of genetically-defined skeletal muscle channelopathies in the Netherlands and report their mutation spectrum. Minimum point prevalence rates were calculated as number of genetically-confirmed skeletal muscle channelopathy patients (CLCN1, SCN4A, CACNA1S and KCNJ2 gene mutations) in the Netherlands (1990-2015) divided by the total number of at-risk individuals. Rates were expressed as cases/100.000 and 95% confidence intervals were calculated based on Poisson distribution. Results of standardized genetic diagnostic procedures were used to analyze mutation spectra. We identified 405 patients from 234 unrelated pedigrees, resulting in a minimum point prevalence of 2.38/100.000 (95% CI 2.16-2.63) for skeletal muscle channelopathies in the Netherlands. Minimum point prevalence rates for the disease groups, non-dystrophic myotonia and periodic paralysis, were 1.70/100.000 and 0.69/100.000 respectively. Sixty-one different CLCN1 mutations (including 12 novel mutations) were detected in myotonia congenita. Twenty-eight different SCN4A missense mutations (including three novel mutations) were identified in paramyotonia congenita/sodium channel myotonia, hypokalemic periodic paralysis and hyperkalemic periodic paralysis. Four different CACNA1S missense mutations were detected in hypokalemic periodic paralysis and five KCNJ2 missense mutations in Andersen-Tawil syndrome. The minimum point prevalence rates for genetically-defined skeletal muscle channelopathies confirm their rare disease status in the Netherlands. Rates are almost twice as high as in the UK and more in line with pre-genetic prevalence estimates in parts of Scandinavia. Future diagnostic and therapeutic studies may benefit from knowledge of the mutation spectrum of skeletal muscle channelopathies.
Assuntos
Síndrome de Andersen/epidemiologia , Canalopatias/epidemiologia , Paralisia Periódica Hipopotassêmica/epidemiologia , Mutação , Miotonia/epidemiologia , Transtornos Miotônicos/epidemiologia , Adulto , Idoso , Síndrome de Andersen/genética , Canais de Cálcio/genética , Canais de Cálcio Tipo L , Canalopatias/genética , Canais de Cloreto/genética , Feminino , Humanos , Paralisia Periódica Hipopotassêmica/genética , Masculino , Pessoa de Meia-Idade , Miotonia/genética , Transtornos Miotônicos/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Países Baixos/epidemiologia , Linhagem , Canais de Potássio Corretores do Fluxo de Internalização/genética , Prevalência , Adulto JovemRESUMO
Recessive mutations in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) were recently shown to cause a motor-predominant Charcot-Marie-Tooth neuropathy. About 80% of the patients exhibit neuromyotonia, a striking clinical and electrophysiological hallmark that can help to distinguish this disease and to guide diagnostic screening. HINT1 neuropathy has worldwide distribution and is particularly prevalent in populations inhabiting central and south-eastern Europe. With 12 different mutations identified in more than 60 families, it ranks among the most common subtypes of axonal Charcot-Marie-Tooth neuropathy. This article provides an overview of the present knowledge on HINT1 neuropathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. We propose diagnostic guidelines to recognize and differentiate this entity and suggest treatment strategies to manage common symptoms. As a recent player in the field of hereditary neuropathies, the role of HINT1 in peripheral nerves is unknown and the underlying disease mechanisms are unexplored. We provide a comprehensive overview of the structural and functional characteristics of the HINT1 protein that may guide further studies into the molecular aetiology and treatment strategies of this peculiar Charcot-Marie-Tooth subtype.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Neuropatia Hereditária Motora e Sensorial/genética , Síndrome de Isaacs/genética , Miotonia/genética , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso Periférico/genética , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/patologia , Neuropatia Hereditária Motora e Sensorial/epidemiologia , Neuropatia Hereditária Motora e Sensorial/patologia , Humanos , Síndrome de Isaacs/epidemiologia , Síndrome de Isaacs/patologia , Miotonia/epidemiologia , Miotonia/patologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/patologiaRESUMO
INTRODUCTION: In acid maltase deficiency (AMD), electrical myotonia (EM) may be restricted to paraspinal muscles. A comprehensive description of the electromyographic (EMG) findings in AMD is lacking. The purpose of this study is to describe the EMG features in adult-onset AMD, focusing on the distribution of EM. METHODS: A retrospective chart review of AMD patients diagnosed at Mayo Clinic over age 18 years. RESULTS: Thirty-seven patients were included. Twenty-eight (76%) had EM in at least 1 muscle, and EM was more common in paraspinal and proximal limb muscles. The tensor fasciae latae (TFL) was equally sensitive to the paraspinals for EM. Three of 4 patients had EM identified in the diaphragm. CONCLUSIONS: Approximately three-quarters of adult-onset AMD patients display EM on EMG. The paraspinal muscles and TFL are the most likely to demonstrate EM, and EM can be detected in the diaphragm of adult onset AMD patients.
Assuntos
Eletromiografia , Doença de Depósito de Glicogênio Tipo II/complicações , Miotonia/diagnóstico , Miotonia/etiologia , Adolescente , Adulto , Idade de Início , Diafragma/fisiopatologia , Feminino , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Miotonia/epidemiologia , Músculos Paraespinais/fisiopatologia , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Myotonic dystrophy type 2 (DM2) is an autosomal dominant inherited disorder with (CCTG)n repeat expansion in intron 1 of the CNBP gene. METHODS: We studied the first 16 Greek DM2 patients who had undergone thorough evaluation. RESULTS: The age at diagnosis ranged from 38 to 69 years. The initial symptoms were proximal weakness, myalgias, and myotonia. Clinical myotonia was elicited in 10 patients, whereas electromyographic myotonic discharges were observed in almost all patients. Subcapsular cataract was frequently present, but cardiac arrhythmias were rare. CONCLUSIONS: In this study of Greek DM2 patients, proximal weakness was the most common initial symptom. Myalgias were also reported in a few patients, yet myotonia was not a major complaint. Although DM2 is considered relatively benign, there are patients who may be affected severely. Thus, a high index of suspicion must be maintained to make a timely diagnosis, especially in those of reproductive age.
Assuntos
Distrofia Miotônica/complicações , Distrofia Miotônica/genética , Fenótipo , Proteínas de Ligação a RNA/genética , Adulto , Idoso , Eletromiografia , Feminino , Grécia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Mialgia/epidemiologia , Mialgia/etiologia , Miotonia/epidemiologia , Miotonia/etiologia , Distrofia Miotônica/etnologia , Estudos RetrospectivosRESUMO
A review on hereditary diseases and/or congenital defects diagnosed in water buffaloes in Brazil is performed. The epidemiological, clinical and pathological aspects of each disease or group of diseases are briefly described. Hereditary diseases include acantholytic mechanobullous dermatosis, arthrogryposis, myotonia, hydranencephaly, chondrodysplasia, and albinism. Congenital defects of unknown cause include megaesophagus, heart defects (patent ductus arteriosus), dermatosparaxia, and different defects of the reproductive system. The breeds most affected by genetic diseases are those from Asian Continent (Murrah and Jafarabadi), probably as a result of inbreeding in Brazilian herds due the prohibition of importation of breeding buffalo from that continent. The diagnosis of two hereditary diseases, arthrogryposis and myotonia, in Rio Grande do Sul (southern Brazil) and Pará (nothern Brazil) suggests that the undesirable genes are widespread in the buffalo population. The identification of these genes by molecular techniques associated with the buffalo breeding with correct sanitary, zootechnical, and reproductive control practices can decrease the negative effects of genetic diseases in the Brazilian buffalo herd.
É realizada uma revisão sobre as doenças hereditárias e/ou defeitos congênitos diagnosticados em búfalos no Brasil. São descritos brevemente os aspectos epidemiológicos, clínicos e patológicos de enfermidades hereditárias ou provavelmente hereditárias já observadas no Brasil, como dermatose mecanobolhosa, artrogripose, miotomia, hidranencefalia, condrodisplasia e albinismo; e dos defeitos congênitos que não tem uma causa ainda comprovada como megaesôfago, defeitos cardíacos (persistência do ducto arterioso), dermatosparaxia, defeitos no sistema reprodutivo e outros defeitos. Observou-se que as raças mais afetadas por enfermidades de natureza genética são as que têm origem no Continente Asiático (Murrah e Jafarabadi), provavelmente em consequência da consanguinidade existente nos rebanhos devido a proibição da importação de reprodutores, sêmen e embriões daquele continente. O diagnóstico de duas dessas doenças, artrogripose e miotomia hereditária no Rio Grande do Sul e no Pará, demonstra que os genes indesejáveis estão disseminados na população de búfalos no país e que a identificação desses genes por meio de técnicas moleculares associada à criação desta espécie com maior controle sanitário, reprodutivo e zootécnico pode minimizar os prejuízos decorrentes dessas enfermidades à bubalinocultura.
Assuntos
Animais , Búfalos/anormalidades , Búfalos/genética , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/veterinária , Albinismo/epidemiologia , Albinismo/veterinária , Anormalidades Congênitas/veterinária , Artrogripose/epidemiologia , Artrogripose/veterinária , Vigilância Sanitária , Hidranencefalia/epidemiologia , Hidranencefalia/veterinária , Miotonia/epidemiologia , Miotonia/veterinária , DermatopatiasRESUMO
OBJECTIVES: To obtain minimum point prevalence rates for the skeletal muscle channelopathies and to evaluate the frequency distribution of mutations associated with these disorders. METHODS: Analysis of demographic, clinical, electrophysiologic, and genetic data of all patients assessed at our national specialist channelopathy service. Only patients living in the United Kingdom with a genetically defined diagnosis of nondystrophic myotonia or periodic paralysis were eligible for the study. Prevalence rates were estimated for England, December 2011. RESULTS: A total of 665 patients fulfilled the inclusion criteria, of which 593 were living in England, giving a minimum point prevalence of 1.12/100,000 (95% confidence interval [CI] 1.03-1.21). Disease-specific prevalence figures were as follows: myotonia congenita 0.52/100,000 (95% CI 0.46-0.59), paramyotonia congenita 0.17/100,000 (95% CI 0.13-0.20), sodium channel myotonias 0.06/100,000 (95% CI 0.04-0.08), hyperkalemic periodic paralysis 0.17/100,000 (95% CI 0.13-0.20), hypokalemic periodic paralysis 0.13/100,000 (95% CI 0.10-0.17), and Andersen-Tawil syndrome (ATS) 0.08/100,000 (95% CI 0.05-0.10). In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees. CONCLUSION: We describe for the first time the overall prevalence of genetically defined skeletal muscle channelopathies in England. Despite the large variety of mutations observed in patients with nondystrophic myotonia and ATS, a limited number accounted for a large proportion of cases.
Assuntos
Canalopatias/epidemiologia , Canalopatias/genética , Músculo Esquelético/fisiologia , Doenças Musculares/epidemiologia , Doenças Musculares/genética , Adulto , Canais de Cloreto/genética , Interpretação Estatística de Dados , Bases de Dados Genéticas , Inglaterra/epidemiologia , Feminino , Humanos , Paralisia Periódica Hipopotassêmica/epidemiologia , Paralisia Periódica Hipopotassêmica/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Mutação/fisiologia , Miotonia/epidemiologia , Miotonia/genética , Transtornos Miotônicos/epidemiologia , Transtornos Miotônicos/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Paralisias Periódicas Familiares/epidemiologia , Paralisias Periódicas Familiares/genética , Paralisia Periódica Hiperpotassêmica/epidemiologia , Paralisia Periódica Hiperpotassêmica/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Prevalência , Canais de Sódio/genética , Canais de Sódio/fisiologia , Reino Unido/epidemiologiaRESUMO
This study assessed the spectrum of disorders associated with electrophysiologic myotonia in a pediatric electromyography laboratory. Records of 2234 patients observed in the Electromyography Laboratory at Boston Children's Hospital from 2000-2011 were screened retrospectively for electrophysiologic diagnoses of myotonia and myopathy. Based on electromyography, 11 patients manifested myotonic discharges alone, eight exhibited both myotonic discharges and myopathic motor unit potentials, and 54 demonstrated myopathic motor unit potentials alone. The final diagnoses of patients with myotonic discharges alone included myotonia congenita, paramyotonia congenita, congenital myopathy, and Pompe disease (acid maltase deficiency). The diagnoses of patients with both myotonic discharges and myopathic motor unit potentials included congenital myopathy and non-Pompe glycogen storage diseases. Myotonic discharges are rarely observed in a pediatric electromyography laboratory, but constitute useful findings when present. The presence or absence of concurrent myopathic motor unit potentials may help narrow the differential diagnosis further.
Assuntos
Eletromiografia/tendências , Miotonia/diagnóstico , Miotonia/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Doenças Musculares/fisiopatologia , Miotonia/epidemiologia , Estudos RetrospectivosRESUMO
We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia. These families represent a distinct phenotype within the spectrum of sodium channel myotonia.
Assuntos
Temperatura Baixa/efeitos adversos , Mutação/genética , Miotonia/epidemiologia , Miotonia/genética , Dor/epidemiologia , Dor/genética , Canais de Sódio/genética , Acetazolamida/uso terapêutico , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Amitriptilina/uso terapêutico , Anticonvulsivantes/uso terapêutico , Bélgica , Carbamazepina/uso terapêutico , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miotonia/etiologia , Canal de Sódio Disparado por Voltagem NAV1.4 , Dor/etiologia , Fenótipo , Resultado do TratamentoRESUMO
Advances in physiology and molecular genetics have promoted greater understanding of the various clinical manifestations of muscle disorders. For example, myotonia or profound weakness may be observed in sodium channel disease (e.g., paramyotonia congenita or hyperkalemic periodic paralysis), depending on the specific channel defect or with slight changes in membrane potential. Observed effects of anesthetic techniques have been essential to elucidating the primary muscular nature of myotonia. Commonly used anesthetic medications have potentially lethal (e.g., MH) or serious (e.g., myotonic dystrophy) adverse effects. Conversely, lidocaine or propofol may have therapeutic benefit for patients with skeletal muscle sodium channel disorders. Additional investigation is required to improve our understanding of how age, gender, or other factors determine the phenotypic expression of malignant hyperthermia. Future research holds the promise for more accurate pre-anesthetic identification of persons with heritable myopathies, especially those who are asymptomatic. Enhanced awareness of multiple organ system involvement in myotonic dystrophy is essential for planning perioperative care. Patients with periodic paralysis require that we know factors that incite or inhibit the development of their attacks. Advances in bench research and detailed clinical studies will further improve our ability to provide optimal care for patients with muscle disorders.
Assuntos
Hipertermia Maligna/terapia , Miotonia/terapia , Animais , Diagnóstico Diferencial , Humanos , Hipercapnia/epidemiologia , Hipercapnia/fisiopatologia , Hipercapnia/terapia , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/epidemiologia , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/epidemiologia , Hipertermia Maligna/fisiopatologia , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Miotonia/epidemiologia , Miotonia/fisiopatologia , Distrofia Miotônica/complicações , Rabdomiólise/diagnóstico , Rabdomiólise/etiologiaRESUMO
Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal muscles with marked hypertrophy in the legs. A transient muscle weakness is particularly pronounced in the arms and hands and is a typical symptom of the disorder. Recently, we showed complete linkage of the disorder GM to the gene (CLCN1) coding for the skeletal muscle chloride channel CLC-1 and the TCRB gene on chromosome 7 in German families. In the study presented here we performed linkage analysis on 14 new GM families. The GM locus was again completely linked to both the CLCN1 and the TCRB gene in all families with a combined lod score of Z = 9.26 at a recombination fraction of theta = 0.00. This confirms our previous data and supports the hypothesis that GM is a genetically homogeneous disorder. The previously detected T to G missense mutation is found on 15% of the 66 GM chromosomes counted so far.
Assuntos
Canais de Cloreto/genética , Cromossomos Humanos Par 7 , Genes Recessivos , Genes , Miotonia/genética , Alelos , Análise Mutacional de DNA , Frequência do Gene , Genes Dominantes , Humanos , Escore Lod , Miotonia/epidemiologia , Miotonia Congênita/genética , Linhagem , Reação em Cadeia da Polimerase , Prevalência , Recombinação GenéticaRESUMO
The epidemiology of neuromuscular diseases was studied in the county of Orebro, Sweden (study population 270,000). Several different sources of data were utilized, compared and validated. On the prevalence of day (January 1, 1988) 474 patients were identified. The rate per 100,000 population was 92 for the postpolio sequelae (PPS) and 84 for the other neuromuscular diseases (motor neuron disease 9, hereditary neuropathies 9, myoneural disorders 16, myotonic disorders 19, muscular dystrophies 20 and myositis 11). Of the patients with the PPS, 80% reported late-onset symptoms. On the basis of an expanded survey including all medical records in one health care district, the prevalence of the PPS was estimated to be 186/100,000 population.
Assuntos
Doenças Neuromusculares/epidemiologia , Síndrome Pós-Poliomielite/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Doença dos Neurônios Motores/epidemiologia , Distrofias Musculares/epidemiologia , Miosite/epidemiologia , Miotonia/epidemiologia , Prevalência , Suécia/epidemiologiaRESUMO
The paper summarizes data on the epidemiology and clinical polymorphism of the major types of myotonias. Presents both familial and sporadic cases of myotonia congenita, atrophica, dystrophica, and Eulenburg's [correction of Eilenburg's] paramyotonias. Describes the clinical picture of Thomsen's disease in childhood. Discusses the types of disease inheritance and nosological entities of myotonias. The material has been obtained from the studies performed over 25 years, which allows the course of the disease to be followed up in families and in individuals, and enables the patients' migration in the region and outside to be traced.
Assuntos
Miotonia/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Miotonia/genética , Miotonia Congênita/epidemiologia , Miotonia Congênita/genética , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/genética , Linhagem , Polimorfismo Genético , Federação Russa/epidemiologiaRESUMO
The incidence of myotonia in the South-West regions of Uzbekistan is 1.6:100000 of the population. Its proportion among other hereditary diseases of the nervous system is 8.2% and among neuromuscular abnormalities--2.6%. Furthermore, it has been also established that an autosomal-recessive form of non-atrophic myotonia is rather prevalent in this region. It has a number of clinical characteristics which differentiate it from a generalized recessive form prevalent in West Europe.