11/50. Exon 17 skipping in CLCN1 leads to recessive myotonia congenita.Mutations in CLCN1, the gene encoding the ClC-1 chloride channel in skeletal muscle, lead to myotonia congenita. The effects on the intramembranous channel forming domains have been investigated more than that at the intracellular C-terminus. We have performed a mutation screen involving the whole CLCN1 gene of patients with myotonia congenita by polymerase chain reaction (PCR), single-strand conformation polymorphism studies, and sequencing. Two unrelated patients harbored the same homozygous G-to-T mutation on the donor splice site of intron 17. This led to the skipping of exon 17, as evidenced by the reverse transcriptase PCR. When the exon 17-deleted CLCN1 was expressed in xenopus oocytes, no chloride current was measurable. This function could be restored by coexpression with the wild-type channel. Our data suggest an important role of this C-terminal region and that exon 17 skipping resulting from a homozygous point mutation in CLCN1 can lead to recessive myotonia congenita.- - - - - - - - - - ranking = 1keywords = muscle (Clic here for more details about this article) |
12/50. Hereditary paroxysmal ataxia with neuromyotonia.The clinical manifestations of a patient with hereditary paroxysmal ataxia and neuromyotonia are described. Generalized tremor, triggered by sudden movements, and spasms of hand and foot muscles were the main clinical findings. Electromyogram (EMG) and nerve blocking studies led to the diagnosis of neuromyotonia. Treatment with acetozolamide was of no therapeutic value, confirming previous observations about the difference in response of paroxysmal ataxia with and without neuromyotonia.- - - - - - - - - - ranking = 1keywords = muscle (Clic here for more details about this article) |
13/50. Novel mutations at carboxyl terminus of CIC-1 channel in myotonia congenita.OBJECTIVES: myotonia congenita (MC), caused by mutations in the muscle chloride channel (CLCN1) gene, can be inherited dominantly or recessively. The mutations at the carboxyl terminus of the CLCN1 gene have been identified in MC patients, but the functional implication of these mutations is unknown. MATERIAL AND methods: Direct sequencing of polymerase chain reaction products covering the whole coding region of the CLCN1 gene was performed in a MC family. This study was designed to investigate the clinical manifestations and genetic analysis of the CLCN1 gene. RESULTS: We identified two novel mutations, 2330delG and 1892C>T, from a genetic screening of the CLCN1 gene in the MC family. The 2330delG mutant allele producing a fs793X truncated protein was identified in a heterozygous state in all the patients. The 1892C>T nucleotide change induced a missense mutation (T631I) found in several asymptomatic individuals, indicating that it may not be associated with MC. Intriguingly, the 2330delG mutation was also found in an asymptomatic subject who also carried the 1892C>T mutation. CONCLUSION: The data indicate that the fs793X mutant protein causes dominantly inherited MC. Because the mutation has been found in a recessive pedigree, the fs793X mutation may have a dual inheritance pattern.- - - - - - - - - - ranking = 1keywords = muscle (Clic here for more details about this article) |
14/50. myotonia congenita--a successful response to carbamazepine.myotonia congenita is a rare disease of skeletal muscle characterized by painless myotonia, generalized muscular hypertrophy and a non-progressive course. We report a 10-year-old girl with myotonia, "Herculean appearance" and electromyographic confirmation of myotonic discharges. There was a dramatic response to carbamazepine. The aim of this report is to make the readers aware of this entity which can be easily controlled with medication and also prevented by genetic counseling.- - - - - - - - - - ranking = 1keywords = muscle (Clic here for more details about this article) |
15/50. paralysis periodica paramyotonica caused by SCN4A Arg1448Cys mutation.paralysis periodica paramyotonica is an overlapping disease that shares the features of paramyotonia characteristic of paramyotonia congenita (PC) and periodic paralysis characteristic of hyperkalemic periodic paralysis. We report the case of a 23-year-old man with paralysis periodica paramyotonica. His father and a younger brother also exhibited a similar phenotype. A SCN4A Arg1448Cys mutation was detected in this family. The affected family members exhibited marked shifts in compound muscle action potential amplitudes on exercise test, and muscle weakness could be induced by potassium loading and cold exposure. This case demonstrates that SCN4A Arg1448Cys can produce paralysis periodica paramyotonica. Other genetic or environmental factors may modulate the manifestation of SCN4A Arg1448Cys mutation.- - - - - - - - - - ranking = 2keywords = muscle (Clic here for more details about this article) |
16/50. Activity-induced weakness in recessive myotonia congenita with a novel (696 1G>A) mutation.OBJECTIVE: To investigate the cause of the transient weakness that occurs in recessive myotonia congenita (RMC) following sustained muscle contraction. methods: Nerve excitability studies were performed on a 35-year-old male with RMC due to a novel 696 1G>A CLCN1 mutation. The median nerve was stimulated at the wrist and compound muscle action potentials (CMAPs) were recorded from abductor pollicis brevis (APB). Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100-ms polarizing currents, a current threshold relationship and the recovery of excitability following supramaximal stimulation were recorded at rest. Excitability parameters were also recorded before and after maximal voluntary contraction (MVC) of APB against resistance for 60s. Results were compared to data obtained from 12 normal controls. RESULTS: Baseline axonal excitability parameters were all normal, indicating that axonal function was normal at the point of stimulation. Following one minute of MVC, excitability parameters demonstrated a significant increase in threshold when compared to controls (RMC 54.9%; controls 15.5 /-3.1%). In the RMC patient, this increase in threshold was associated with a 39% reduction in the amplitude of the maximal CMAP, which remained unaffected in controls. CONCLUSIONS: The reduction in maximal CMAP is likely to represent muscle activation failure due to depolarization block, with the increase in threshold possibly reflecting a compensatory attempt by motor axons to overcome prolonged contraction-induced changes in the muscle membrane. SIGNIFICANCE: The prolonged recovery of excitability following sustained muscle contraction is likely to be a contributing factor to symptoms of weakness and fatigue experienced by RMC patients.- - - - - - - - - - ranking = 5keywords = muscle (Clic here for more details about this article) |
17/50. myotonia congenita--a cause of muscle weakness and stiffness.BACKGROUND: A 56-year-old woman was referred to a neurogenetic clinic with a history of stiffness and transient weakness. A previous needle electromyogram had confirmed the presence of myotonia, but a muscle biopsy had revealed no evidence of dystrophy. INVESTIGATIONS: Neurological examination, electrophysiological studies and genetic testing. diagnosis: Recessive myotonia congenita (Becker's disease). MANAGEMENT: Explanation of the nature of the disease and treatment with mexiletine 200 mg twice daily.- - - - - - - - - - ranking = 5keywords = muscle (Clic here for more details about this article) |
18/50. Case-of-the-month: autosomal recessive myotonia congenita: marked muscle weakness in a 16-year-old boy.A 16-year-old boy had a 10-year history of stiffness in leg muscles. There was marked weakness of neck flexors, shoulder abductors, and ankle dorsiflexors, with hypertrophy of most muscle groups and both action and percussion myotonia. The parents were normal. Motor unit potential mean duration was reduced in the weakest muscle (tibialis anterior), and a biopsy of the same muscle showed only minimal abnormalities. Exercise and repetitive stimulation (30 Hz) of the tibialis anterior disclosed a decline in the compound muscle action potential that appeared to correlate with the muscular weakness.- - - - - - - - - - ranking = 9keywords = muscle (Clic here for more details about this article) |
19/50. Neuromyotonia in hereditary motor neuropathy.Two siblings with a distal motor neuropathy experienced cramping and difficulty in relaxing their muscles after voluntary contraction. Electromyographic recordings at rest revealed repetitive high voltage spontaneous electrical discharges that were accentuated after voluntary contraction and during ischaemia. Regional neuromuscular blockage with curare indicated hyperexcitability of peripheral nerve fibres and nerve block suggested that the ectopic activity originated in proximal segments of the nerve. Symptoms were improved with diphenylhydantoin, carbamazepine and tocainide.- - - - - - - - - - ranking = 18.393027641483keywords = cramp, muscle (Clic here for more details about this article) |
20/50. myotonia congenita, klinefelter syndrome and primary hypoparathyroidism: the first report of the unusual combination of three rare diseases in the literature.The first report of the rare combination of myotonia congenita, klinefelter syndrome and primary hypoparathyroidism was reported. The patient was a 21-year-old man who presented with stiffness of the muscles for 12 years and a history of generalised convulsion for 8 years. His school studies declined gradually and his secondary schooling was interrupted. Examination revealed a muscular young man with myotonic percussion over the muscles of the body as well as the myotonic lid lag. Chvostek's sign was positive and his serum calcium level was very low whereas the serum phosphate was high. Symmetrical and extensive calcification of the brain parenchyma was demonstrated in the CT scan. His secondary sexual characteristics were not well developed and his testes were very small. Chromosome study confirmed the diagnosis of klinefelter syndrome by the identification of 47 XXY chromosome. He was prescribed calcium replacement and the anticonvulsant was withheld with no more episodes of seizure.- - - - - - - - - - ranking = 2keywords = muscle (Clic here for more details about this article) |
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