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Ion channel disorders
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Tuesday, July 9, 2002
P-269 Quantitative Kinematic Analysis of Oropharyngeal Swallow in Patients with Inflanunaotry Myopathy Nam-Jong Paik*, Sang-Joon Kim, Ho-Joon Lee, Tai Ryoon Ham Seoul,
Republic of Korea Objective: In all forms of inflammatory myopathy, pharyngeal and neckflexor muscles are often involved, causing dysphagia. This investigation compared the biomechanical characteristics of oropharyngeal swallow between dysphagic inflammatory myopathy patients and non-dysphagic normal people. Method: Videofluoroscopic findings of three dysphagic patients diagnosed with the inflammatory myopathy and five non-dysphagic normal people were analyzed using 2-D motion analysis system. The anterior and vertical movement of the hyoid bone, the angular motion of the epiglottis and the diameter of the upper airway entrance opening during swallow were compared. Results: Inflammatory myopathy patients exhibited significantly reduced maximum anterior and vertical hyoid movement as compared to the normal people. The anteriror and vertical hyoid movement were 0.284- 0.10 cm, 0.54 4- 0.31 cm in inflammatory myopathy as compared to 1.98 40.29 cm, 2.27 4- 0.48 cm in normal. The angular motion of the epiglottis were 27.36 4- 11.53 ° in inflammatory myopathy as compared to 97.08 411.03 ° in normal. The minimum diameter of the upper airway entrance opening were 0.58 4- 0.13 cm in inflammatory myopathy as compared to 0 cm in normal people. Conclusions: The biomechanical characteristics of the oropharyngeal swallow in dysphagic patients with inflammatory myopathy were different from non-dysphagic normal people. These data support the hypothesis of reduced muscle reserve in the swallows of inflammatory myopathy patients. This quantitative kinematic analysis of oropharyngeal swallow could be used as a tool for evaluating the effect of swallowing trainings in these patients.
P-270 Missed Diagnosis of Childhood Dermatomyositis (JDM)
Poster Presentations
Ion Channel Disorders P-271 Genetic Expression Profiling in Muscle from Sodium Channel 8 Alpha (SCN8A) Null Mice P. Cote * 1, C. Jacobson 2, 1y. DeRepentigny, S.R Levinson 3, D. Duggan 2, R. Kothary 1. 1Ottawa, Canada; 2Bethesda, USA; 3Denve~ USA;
Objective: A novel spontaneous mouse mutant, named degenerating muscle (dmu) because of its prominent skeletal and cardiac muscle degeneration, has been identified in our laboratory. The autosomal recessive mutation causes an early-onset progressive paralysis of the hind limbs, weakness, and lethality in the first month of life. Using cDNA microarrays we will identify mechanisms involved in muscle degeneration in dmu mutant mice. Methods: Total RNA was isolated from skeletal and cardiac muscle dissected from mutant mice as well as wild-type littermates before (P5) and after (P15) the manifestation of the phenotype. The RNA was then processed, labeled and hybridized to cDNA microarrays. The resulting data was analyzed using FileMaker Pro (Claris) and GeneSpring (Silicon Genomics) software. Results: We have mapped the mutation to the distal portion of chromosome 15, a region that is syntenic to chromosome 12q13. dmu mice have recently been found to have a mutation in the voltage gated sodium channel subunit ScnSa and thus to be a novel allele of motor-endplate disease (med). Conclusion: Although ScnSa-null mice have been defined as being 'functionally denervated' they have a muscle degeneration that is uncharacteristic of what is observed in surgical denervation experiments. These expression profiling experiments will enable us to dissect the pathways involved in neuropathologically induced muscle degeneration.
P-272 Andersen's Syndrome: A Skeletal Muscle Potassium Channel Disorder
A. Spiro*. Bronx, NY,, USA
N.P. Davies*, A. Weber, R. Mueller, D. Hilton-Jones, P.F. Chinnery, M.G. Hanna. Oxford, UK
Objective: The purpose of this study is to investigate factors in the clin-
Background: Andersen's syndrome is a triad of periodic paralysis (hypo-
ical and/or laboratory studies which led clinicians to miss or delay the diagnosis of JDM. Methods: The clinical and laboratory investigations of the author's recent personal cases of JDM with confirmed muscle biopsy diagnosis were tabulated and assessed for individual or mukiple factors which led to delay in recognition of JDM or to a wrong diagnosis. Results: In one case, despite a rather typical pattern of JDM, the electromyography (EMG)was misinterpreted as indicating denervation, prompting the referral of the child for DNA studies for spinal muscular atrophy. In other cases the creatine kinase (CK) values and/or sedimentation rates (ESR) were normal, which led to delay in referral. In one child the lack of pain and rash led to a mistaken diagnosis of muscular dystrophy, and, in others, to an original impression of psychogenic weakness. In one child who had been a premature baby, new onset of weakness led to a mistaken diagnosis of cerebral palsy. Conclusions: As pointed out by various authors strict criteria to establish a diagnosis of JDM must be modified. The clinical picture must be carefully ascertained and coupled with the constellation of laboratory investigations. Lack of pain, normal CK and ESR, lack of typical rash and, when performed, lack of characteristic features on EMG do not necessarily exclude a diagnosis of JDM in the face of new onset proximal muscle weakness in children. Early diagnosis can lead to effective treatment. Details will be discussed.
or hyper-), malignant ventricular arrhythmias and dysmorphism. The syndrome is often overlooked as the dysmorphism is subtle and the ventricular arrhythmias may not become symptomatic until later in the disease course. Mutations in a voltage-independent skeletal muscle potassium channel gene (KCNJ2) were recently shown to cause this disorder. Methods: We identified 3 families with clinical features consistent with Andersen's syndrome. In addition to detailed clinical examination each patient underwent neurophysiological and cardiological investigations. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control chromosomes (160) were screened using restriction digests. Results: Each family harboured a new pathogenic point mutation within KCNJ2. In family A, an aspartic acid was substituted for a glycine at codon (G300D) in the carboxy-terminal of the channel. Family B and C harboured mutations in the amino-terminal (D78G, R67W). Conclusion: Andersen's syndrome should be considered in any patient with hypo- or hyper-kalaemic periodic paralysis. The ventricular arrhythmias may post date the onset of the paralytic episodes by years but the ECG often shows a long QT interval early on in the disorder. We have identified 3 new disease-causing mutations in KCNJ2, demonstrating that DNA-based diagnosis is possible in this disorder. It is important to note that non-penetrance occurs in this disorder and there is a high de novo mutation rate.
Tuesday, July 9, 2002
P-269 Quantitative Kinematic Analysis of Oropharyngeal Swallow in Patients with Inflanunaotry Myopathy Nam-Jong Paik*, Sang-Joon Kim, Ho-Joon Lee, Tai Ryoon Ham Seoul,
Republic of Korea Objective: In all forms of inflammatory myopathy, pharyngeal and neckflexor muscles are often involved, causing dysphagia. This investigation compared the biomechanical characteristics of oropharyngeal swallow between dysphagic inflammatory myopathy patients and non-dysphagic normal people. Method: Videofluoroscopic findings of three dysphagic patients diagnosed with the inflammatory myopathy and five non-dysphagic normal people were analyzed using 2-D motion analysis system. The anterior and vertical movement of the hyoid bone, the angular motion of the epiglottis and the diameter of the upper airway entrance opening during swallow were compared. Results: Inflammatory myopathy patients exhibited significantly reduced maximum anterior and vertical hyoid movement as compared to the normal people. The anteriror and vertical hyoid movement were 0.284- 0.10 cm, 0.54 4- 0.31 cm in inflammatory myopathy as compared to 1.98 40.29 cm, 2.27 4- 0.48 cm in normal. The angular motion of the epiglottis were 27.36 4- 11.53 ° in inflammatory myopathy as compared to 97.08 411.03 ° in normal. The minimum diameter of the upper airway entrance opening were 0.58 4- 0.13 cm in inflammatory myopathy as compared to 0 cm in normal people. Conclusions: The biomechanical characteristics of the oropharyngeal swallow in dysphagic patients with inflammatory myopathy were different from non-dysphagic normal people. These data support the hypothesis of reduced muscle reserve in the swallows of inflammatory myopathy patients. This quantitative kinematic analysis of oropharyngeal swallow could be used as a tool for evaluating the effect of swallowing trainings in these patients.
P-270 Missed Diagnosis of Childhood Dermatomyositis (JDM)
Poster Presentations
Ion Channel Disorders P-271 Genetic Expression Profiling in Muscle from Sodium Channel 8 Alpha (SCN8A) Null Mice P. Cote * 1, C. Jacobson 2, 1y. DeRepentigny, S.R Levinson 3, D. Duggan 2, R. Kothary 1. 1Ottawa, Canada; 2Bethesda, USA; 3Denve~ USA;
Objective: A novel spontaneous mouse mutant, named degenerating muscle (dmu) because of its prominent skeletal and cardiac muscle degeneration, has been identified in our laboratory. The autosomal recessive mutation causes an early-onset progressive paralysis of the hind limbs, weakness, and lethality in the first month of life. Using cDNA microarrays we will identify mechanisms involved in muscle degeneration in dmu mutant mice. Methods: Total RNA was isolated from skeletal and cardiac muscle dissected from mutant mice as well as wild-type littermates before (P5) and after (P15) the manifestation of the phenotype. The RNA was then processed, labeled and hybridized to cDNA microarrays. The resulting data was analyzed using FileMaker Pro (Claris) and GeneSpring (Silicon Genomics) software. Results: We have mapped the mutation to the distal portion of chromosome 15, a region that is syntenic to chromosome 12q13. dmu mice have recently been found to have a mutation in the voltage gated sodium channel subunit ScnSa and thus to be a novel allele of motor-endplate disease (med). Conclusion: Although ScnSa-null mice have been defined as being 'functionally denervated' they have a muscle degeneration that is uncharacteristic of what is observed in surgical denervation experiments. These expression profiling experiments will enable us to dissect the pathways involved in neuropathologically induced muscle degeneration.
P-272 Andersen's Syndrome: A Skeletal Muscle Potassium Channel Disorder
A. Spiro*. Bronx, NY,, USA
N.P. Davies*, A. Weber, R. Mueller, D. Hilton-Jones, P.F. Chinnery, M.G. Hanna. Oxford, UK
Objective: The purpose of this study is to investigate factors in the clin-
Background: Andersen's syndrome is a triad of periodic paralysis (hypo-
ical and/or laboratory studies which led clinicians to miss or delay the diagnosis of JDM. Methods: The clinical and laboratory investigations of the author's recent personal cases of JDM with confirmed muscle biopsy diagnosis were tabulated and assessed for individual or mukiple factors which led to delay in recognition of JDM or to a wrong diagnosis. Results: In one case, despite a rather typical pattern of JDM, the electromyography (EMG)was misinterpreted as indicating denervation, prompting the referral of the child for DNA studies for spinal muscular atrophy. In other cases the creatine kinase (CK) values and/or sedimentation rates (ESR) were normal, which led to delay in referral. In one child the lack of pain and rash led to a mistaken diagnosis of muscular dystrophy, and, in others, to an original impression of psychogenic weakness. In one child who had been a premature baby, new onset of weakness led to a mistaken diagnosis of cerebral palsy. Conclusions: As pointed out by various authors strict criteria to establish a diagnosis of JDM must be modified. The clinical picture must be carefully ascertained and coupled with the constellation of laboratory investigations. Lack of pain, normal CK and ESR, lack of typical rash and, when performed, lack of characteristic features on EMG do not necessarily exclude a diagnosis of JDM in the face of new onset proximal muscle weakness in children. Early diagnosis can lead to effective treatment. Details will be discussed.
or hyper-), malignant ventricular arrhythmias and dysmorphism. The syndrome is often overlooked as the dysmorphism is subtle and the ventricular arrhythmias may not become symptomatic until later in the disease course. Mutations in a voltage-independent skeletal muscle potassium channel gene (KCNJ2) were recently shown to cause this disorder. Methods: We identified 3 families with clinical features consistent with Andersen's syndrome. In addition to detailed clinical examination each patient underwent neurophysiological and cardiological investigations. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control chromosomes (160) were screened using restriction digests. Results: Each family harboured a new pathogenic point mutation within KCNJ2. In family A, an aspartic acid was substituted for a glycine at codon (G300D) in the carboxy-terminal of the channel. Family B and C harboured mutations in the amino-terminal (D78G, R67W). Conclusion: Andersen's syndrome should be considered in any patient with hypo- or hyper-kalaemic periodic paralysis. The ventricular arrhythmias may post date the onset of the paralytic episodes by years but the ECG often shows a long QT interval early on in the disorder. We have identified 3 new disease-causing mutations in KCNJ2, demonstrating that DNA-based diagnosis is possible in this disorder. It is important to note that non-penetrance occurs in this disorder and there is a high de novo mutation rate.