Neuromuscular disorders : NMD
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Paramyotonia congenita (OMIM 168300) is a non-dystrophic myopathy caused by mutations in the SCN4A gene that sometimes can be confused with myotonia congenita. Another disease also caused by mutations in the gene SCN4A is called myotonia aggravated by potassium (OMIM 170500, 613345). ⋯ In this study we present a case of paramyotonia congenita in a family with several affected members and in which a mutation in the SCN4A gene was identified. Evolutionary conservation data and predictive algorithms of pathogenicity allow us to conclude that this DNA variant is the cause of the disease in this family.
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Neuromuscul. Disord. · May 2017
Resequencing array for gene variant detection in malignant hyperthermia and butyrylcholinestherase deficiency.
Malignant hyperthermia (MH) and butyrylcholinestherase (BCHE) deficiency are two relevant pharmacogenetic disorders in anesthetic practice linked with sequence variants, the former in the RyR1 and CACNA1S genes, the latter in the BCHE gene. Genotyping for known pathogenic variants in these genes is useful to help identify susceptible individuals, and others may exist but remain unknown, because full-length sequence of these genes is, in general, not investigated. To facilitate this task, we developed a resequencing DNA array, the perioperative patient safety (POPS) array, to be able to screen the entire coding sequences of the RyR1, CACNA1S and BCHE genes. ⋯ Detection of 29 predetermined RyR1 variants in 44 individuals was successful in 97% of the cases, among them all 16 variants of established diagnostic value. In a trial application of the arrays, 21 MH-susceptible subjects with no known RyR1 or CACNA1S variants were screened, resulting in the discovery of new variants, all confirmed by capillary sequencing. In conclusion, arrays offer an efficient high-throughput alternative for diagnostic genotyping of candidate genes affecting MH susceptibility, BCHE deficiency and other neuromuscular disorders, simultaneously enabling a comprehensive search for rare variants in these genes.
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Neuromuscul. Disord. · Apr 2017
Multicenter StudyCharacterization of pulmonary function in 10-18 year old patients with Duchenne muscular dystrophy.
Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). ⋯ Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: -8.9% [SD 2.0]; FVC%p: -8.7% [SD 1.1]; FEV1%p: -10.2% [SD 2.0]) than static airway pressures (MIP%p: -4.5 [SD 1.3]; MEP%p: -2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase.
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Neuromuscul. Disord. · Jan 2017
Case ReportsSuccessful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report.
Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. ⋯ Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG.
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Neuromuscul. Disord. · Aug 2016
Observational StudyProgression from respiratory dysfunction to failure in late-onset Pompe disease.
To identify determinants of respiratory disease progression in late-onset Pompe disease (LOPD), we studied relationships between pulmonary function, respiratory muscle strength, gas exchange, and respiratory control. Longitudinal evaluation of 22 LOPD patients (mean age 38 years) was performed at 6-month intervals for 6-24 months. Measurements included vital capacity (VC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), tidal volume (VT), dead space (VD), and ventilatory response to CO2. ⋯ The presence of hypercapnia and/or ventilatory support was associated with reduced ventilatory responsiveness to CO2 (≤0.7 l/min/mmHg). We conclude that daytime hypercapnia, an indicator of chronic respiratory failure, is tightly linked to the degree of respiratory muscle weakness and severity of pulmonary dysfunction in LOPD patients. Reductions in CO2 clearance efficiency and ventilatory responsiveness may contribute to the development of chronic daytime hypercapnia.