1/42. Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.malignant hyperthermia (MH) in man is an autosomal dominant disorder of skeletal muscle Ca(2 )-regulation. During anesthesia in predisposed individuals, it is triggered by volatile anesthetics and depolarizing muscle relaxants. In >50% of the families, MH susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum, on chromosome 19q12-13.2. To date, 21 RYR1 mutations have been identified in a number of pedigrees. Four of them are also associated with central core disease (CCD), a congenital myopathy. Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg. In one CCD family, the disease was caused by a recently reported MH mutation, Arg-2454-His. Two novel mutations, Thr-2206-Arg and Arg-2454-Cys were detected, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations cosegregation between genetic result and IVCT was almost perfect, only three genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembraneous region of RYR1 did not yield a new mutation confirming the cytosolic portion of the protein to be of main functional importance for disease pathogenesis.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/42. Suxamethonium-induced rhabdomyolysis in a healthy middle-aged man.A 43-year-old man developed rhabdomyolysis after uvulo- palatopharyngoplasty. After induction with thiopentone and suxamethonium the anesthesia was maintained with halothane. The patient responded to treatment and made an uneventful recovery. In earlier reports of rhabdomyolysis after general anaesthesia with halothane and suxamethonium almost all the patients had malignant hyperthermia (MH) or muscular dystrophy. About 50% of malignant hyperthermia patients carry a mutation in the RYR1 gene. Our patient did not have mutations in the four MH-associated genes tested, but the total amount of different mutations is by now about twenty. Therefore, despite these negative tests rhabdomyolysis may be a sign of subclinical malignant hyperthermia which cannot be ruled out by our investigations. This rare case of rhabdomyolysis in a healthy man suggests careful monitoring of the patient when-ever suxamethonium is used.- - - - - - - - - - ranking = 9.6920066511265keywords = muscular dystrophy, dystrophy (Clic here for more details about this article) |
3/42. malignant hyperthermia susceptibility revealed by myalgia and rhabdomyolysis during fluoroquinolone treatment.fluoroquinolones cause myalgia, but this complication is not clearly documented. We describe a patient who developed myalgia and rhabdomyolysis during fluoroquinolone treatment. The patient was a 33-year-old man treated with norfloxacin for common cystitis. He complained of general muscular fatigue, tendon disorders, and articular pain during treatment. When the antimicrobial agent was stopped, symptoms decreased, with persistence of slight myalgia for 10 days. rhabdomyolysis was detected. Six months later, investigation by 31P magnetic resonance spectroscopy revealed an oxidative disorder and an abnormal abundance of phosphomonoesters. in vitro contracture tests led to a diagnosis of malignant hyperthermia susceptibility. Our case shows that for any subject presenting myalgia with rhabdomyolysis triggered by fluoroquinolone treatment, the presence of a latent myopathy should be investigated.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
4/42. Intolerance to neuroleptics and susceptibility for malignant hyperthermia in a patient with proximal myotonic myopathy (PROMM) and schizophrenia.We report a patient with proximal myotonic myopathy who was treated with neuroleptics because of exacerbating schizophrenia. Under therapy with fluanxol, the patient developed muscle stiffness and oculogyric cramps. Treatment with both amisulpride and olanzapine lead to markedly elevated serum creatine kinase levels. An in-vitro contracture test was positive for halothane. Thus, in patients with all kinds of multisystemic myotonic myopathies, a susceptibility for malignant hyperthermia and intolerance towards neuroleptics should be taken into account.- - - - - - - - - - ranking = 5keywords = myopathy (Clic here for more details about this article) |
5/42. King syndrome in pregnancy.BACKGROUND: King syndrome is characterized by the presence of a nonspecific myopathy, a susceptibility to malignant hyperthermia, and dysmorphic features similar to the phenotype seen in noonan syndrome. CASE: A young primigravida with King syndrome presented at 19 weeks' gestation. The patient required nocturnal mechanical ventilation via tracheostomy, and there was concern that the patient would become increasingly dependent on mechanical ventilation during pregnancy. The patient underwent a forceps-assisted delivery at 35 weeks' gestation, and both the patient and her infant did well and were discharged on postpartum day 3. CONCLUSION: In the gravida with King syndrome, agents that may trigger malignant hyperthermia should be avoided. Significant myopathy may result in respiratory compromise, and a multidisciplinary approach is necessary to optimize maternal and fetal outcome.- - - - - - - - - - ranking = 2keywords = myopathy (Clic here for more details about this article) |
6/42. Anesthetic management of a ventilator-dependent parturient with the King-Denborough syndrome.PURPOSE: The King-Denborough syndrome (KDS) is a rare disorder that is associated with myopathy, susceptibility to malignant hyperthermia (MH) as well as congenital skeletal and facial anomalies. We report the anesthetic management of a parturient with KDS. Clinical features: We describe the management of a 24-yr-old primiparous woman with a diagnosis of KDS and a history of previous MH reaction (age two). Her KDS resulted in chronic respiratory failure. She had a permanent tracheostomy and required overnight ventilatory support for the previous two years. She had three admissions during her pregnancy, one for pneumonia and two for preterm labour. Labour was induced at 37 weeks. Her labour was managed in the operating room where a "clean" anesthesia machine was ready. Cooling aids and a MH emergency kit were immediately available. Intravenous access, an arterial line and a lumbar epidural catheter were inserted before induction of labour. Ropivacaine 0.08% fentanyl 2 microg x mL(-1) were used for patient-controlled epidural analgesia. After 6.5 hr of labour the patient required ventilation. An outlet forceps was performed for delivery. Postpartum, she was ventilated overnight in the intensive care unit. CONCLUSION: The use of epidural analgesia, close monitoring and collaboration between the various disciplines were important in achieving a safe and uneventful labour in this high-risk parturient.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
7/42. Chronic myopathy in a patient suspected of carrying two malignant hyperthermia susceptibility (MHS) mutations.malignant hyperthermia (MH) is a pharmacogenetic myopathy triggered by a variety of anaesthetic agents and muscle relaxants. In humans, susceptibility to MH is inherited as an autosomal dominant trait, and susceptible patients do not show a clinically relevant myopathy unless having suffered from a MH crisis. Homozygosity for the MHS trait is thought to be an uncommon finding, and so far only a few cases of patients suggested to be homozygous for MH on the basis of pedigree information were reported and described as having a more severe form of this condition resulting in clinical symptoms also in the absence of triggering agents. We report clinical findings in a patient with chronic myopathy beginning at the age of 2 yr and associated with a number of unique features, the most important being a family history of MHS present in both parents. She became symptomatic with marked muscular weakness and elevated serum CK levels. A muscle biopsy showed a distinct enlargement and increase of muscle mitochondria. In the in vitro contracture test the patient's muscle responded with unusually high contractures already at basal levels of triggering agents indicating a particularly severe MHS condition. dna markers for the MHS1 locus, described previously on chromosome 19q12-13.2 in Irish and Canadian pedigrees, could not be used to confirm her homozygous state because our molecular genetic studies had previously excluded the MHS trait in this pedigree from this locus.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 7keywords = myopathy (Clic here for more details about this article) |
8/42. Myogenes and myotubes.Investigation of the congenital myopathies has been limited by a lack of knowledge regarding basic mechanisms involved in normal myogenesis of human muscle and the relative rarity of these diseases. A newly recognized family of regulatory genes has been shown to be necessary for myogenesis to proceed to formation of normal mature muscle. It is likely that investigation of patients with one or more types of structural myopathy may show that abnormalities of the regulatory basic helix-loop-helix (bHLH) genes may be responsible for disease.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
9/42. King syndrome: a genetically heterogenous phenotype due to congenital myopathies.We report on a patient with myopathy, kyphoscoliosis, joint contractures, and a facial appearance consistent with King syndrome. Unlike other reported cases, our patient had hyperextensible joints, normal stature, and pectus excavatum. The cardiac ventricles, aorta, and pulmonary artery were dilated. malignant hyperthermia did not occur under anaesthesia although there was a transient increase in CK levels. Muscle bulk and tone were significantly decreased but collagen and elastin fibres were normal. The variable clinical presentation of King syndrome suggests that the manifestations are caused by different congenital myopathies and in all cases there is probably an increased risk of malignant hyperthermia.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
10/42. Multi-minicore disease with susceptibility to malignant hyperthermia in pregnancy.Multi-minicore disease (MmD) is a congenital non-progressive or slowly progressive myopathy associated with multifocal degeneration of muscle fibers. Obstetric management for patients with MmD has not been described previously. A 25-year-old primigravida with a history of muscular weakness from birth was diagnosed with MmD and found to be susceptible to malignant hyperthermia (MH) by muscle biopsy at 28 weeks of gestation. pregnancy proceeded uneventfully and she had a successful vaginal delivery under sufficient preparation for the possible occurrence of MH. pregnant women who exhibit myopathic symptoms from childhood should consult an anesthesiologist prior to delivery.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
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