Distrofia miotónica de Steinert. Presentación de un caso / Steinert’s Myotonic Dystrophy. Case Presentation

Frecuentemente la insuficiencia cardiaca es la consecuencia final de diversas enfermedades cardiovasculares; pero en raros casos no sucede así, ya que se reconocen otras causas menos frecuentes por daño miocárdico. Puede ser el resultado de algunos trastornos genéticos, representados por algunas miocardiopatías, hemoglobinopatías, desórdenes mendelianos de la matriz extracelular y enfermedades neuromusculares. Estas últimas incluyen una enfermedad muy poco frecuente, con herencia autosómica dominante, conocida como distrofia miotónica tipo 1 o enfermedad de Steinert. Esta enfermedad se caracteriza por la variabilidad de su expresión, que incluye afectación cardiaca. Se presenta el caso de un paciente atendido en Servicio de Urgencias y Emergencias, con disnea marcada, insuficiencia cardiaca y sin factores de riesgo cardiovascular identificados. En el examen clínico se constató arritmia, distrofia muscular, calvicie y signos miotónicos. Después de realizar algunos exámenes se concluyó con el diagnóstico de miotonía de Steinert. El interés de esta comunicación radica en que se trata de una enfermedad rara; incluso, puede ser de utilidad en el contexto docente.

Heart failure is frequently the final consequence of diverse cardiovascular diseases, but in rare cases it does not happen because some other infrequent causes are identified for myocardial damage. It may be the result of some genetic disorders, represented by some myocardiopathies, hemoglobinopathies, mendelian disorders of the extracellular matrix and neuromuscular diseases. The last ones include an infrequent disease, autosomal dominant inheritance, known as myotonic dystrophy type 1 or Steinert’s disease. This disease is characterized by the variability in its presentation, which include cardiac involvement. A case treated at the Emergency and Urgency Service is presented with marked dyspnea, cardiac failure and without identified cardiovascular risk factors. On clinical examination it was observed arrhythmia, muscular dystrophy, baldness and myotonic signs. After analyzing some tests it was concluded with a diagnosis of Steinert’s Myotonia. The interest of this communication is that it is in relation with a rare disease; it may even be useful in the teaching context.

Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy

BACKGROUND AND PURPOSE: Mutations of the skeletal muscle sodium channel gene SCN4A, which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenita (PMC), potassium-aggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. METHODS: Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. RESULTS: We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure myotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. CONCLUSIONS: Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

A paralysis periodica paramyotonia congenital pedigree: clinic and molecular genetic studies / 中华神经科杂志

Objective To report clinical symptoms of a Chinese pedigree of familial paramyotonia congenital (PMC) with progressive myopathy (PM), and investigate the mutations of hot spots in the adult skeletal muscle sodium channel α-subunit (SCN4A). Methods The medical history and clinical phenotype of the patients from this large family with PMC were collected. Insertional and spontaneous activity were recorded by routine electromyograph (EMG), and the exercise test (ET) and cool water test were also performed on some patients during episodes. The mutations of SCN4A were screened by PCR-SSCP and DNA sequencing in affected and unaffected members. Results The family is a four-generation kindred with 15 members affected by severe, homogeneous paralysis periodiea paramyotoniea pheuotype. The onset was early, and almost all patients developed severe progressive myopathy by middle age. Routine EMG shows myotonia discharge in all affected subjects. The compound remarkably motor action potential (CMAP) decreased more than 40% after ET with greater decreases in cool water test than in ET. The mutation screening study revealed a missense mutation (Met1592Val) in SCN4A in patients. Conclusions Autosomal dominant inheritance pattern with complete penetrance was observed in this family. The phenotype is in accord with that reported in other ethnic populations with more severe symptoms. The ET and cool water tests may be used as an easy and reliable diagnostic method. Our research supports that periodic paralysis and paramyotonia can be caused by the same mutation in SCN4A. Mutation Met1592Val is a hotspot for mutation screening in patients with PMC accompanied by PM in the Chinese population.

A Korean Family with Arg1448Cys Mutation of SCN4A Channel Causing Paramyotonia Congenita: Electrophysiologic, Histopathologic, and Molecular Genetic Studies

A family with paramyotonia congenita (PC) is presented. At least 10 family members were affected in an autosomal dominant inheritance pattern. The proband had cold-sensitive muscle stiffness, paradoxical myotonia, and intermittent muscle weakness since childhood. The serum level of creatine kinase was mildly elevated and short exercise test with cooling revealed a drastic reduction of compound muscle action potentials with repetitive discharges. Muscle biopsy revealed marked variation in the fiber size and increased internal nuclei. The molecular biological study revealed a common missense mutation (Arg1448Cys) at the voltage-gated sodium channel gene (SCN4A). The repetitive CMAP discharges during short exercise test with cooling observed in the proband has not been reported previously. This observation needs to be confirmed among PC patients with different mutations. This is the first report on a PC family confirmed by the molecular biological technique in Korea.