Andersen-Tawil Syndrome with High Risk of Sudden Cardiac Death in Four Mexican Patients. Cardiac and Extra-Cardiac Phenotypes

ABSTRACT Background: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incomplete penetrance and variable expression that result in a challenging diagnosis. Objective: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. Methods: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. Results: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier’s scale. Conclusions: Extra-cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

Andersen-Tawil Syndrome with High Risk of Sudden Cardiac Death in Four Mexican Patients. Cardiac and Extra-Cardiac Phenotypes.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incom- plete penetrance and variable expression that result in a challenging diagnosis. OBJECTIVE: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. METHODS: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. RESULTS: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier's scale. CONCLUSIONS: Extra- cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

[Implementation of intraoperative neurophysiologic monitoring in children and adults in secondary and tertiary health care facilities]. / Implementación del monitoreo neurofisiológico intraoperatorio en niños y adultos en el segundo y tercer nivel de atención.

INTRODUCTION: Intraoperative neurophysiological monitoring (IONM) is a procedure that uses neurophysiological techniques in order to evaluate the motor and sensitive systems during surgeries that endanger the nervous system. METHOD: The approach, scope, target population, and clinical questions to be answered were defined. A systematic search of the evidence was conducted step by step; during the first stage, clinical practice guidelines were collected, during the second stage systematic reviews were obtained, and during the third stage, clinical trials and observational studies were procured. The MeSH nomenclature and free related terminology were used, with no language restrictions and a 5-10 years frame. The quality of the evidence was graded using the CEPD and SIGN scales. RESULTS: Obtained using the search algorrhythms of 892 documents. Fifty-eight were chosen to be included in the qualitative synthesis. A meta-analysis was not possible due to the heterogeneity of the studies. CONCLUSIONS: Eighteen recommendations were issued and will support the adequate use of the IONM.

INTRODUCCIÓN: El monitoreo neurofisiológico intraoperatorio (MNIO) es un procedimiento que emplea técnicas neurofisiológicas con la finalidad de evaluar los sistemas motor y sensitivo durante cirugías que ponen en riesgo al sistema nervioso. MÉTODO: Se definieron el enfoque, los alcances, la población diana y las preguntas clínicas por resolver. Se realizó una búsqueda sistematizada de la evidencia por etapas. En la primera, se buscaron guías de práctica clínica; en la segunda, revisiones sistemáticas; y en la tercera, ensayos clínicos y estudios observacionales. Se utilizaron los términos MeSH y libres correspondientes, sin restricciones de lenguaje y con una temporalidad de 5 a 10 años. Se graduó la calidad de la evidencia utilizando las escalas CEPD y SIGN. RESULTADOS: Mediante los algoritmos de búsqueda se obtuvieron 892 documentos, y se seleccionaron 58 para la inclusión de la síntesis cualitativa. Debido a la heterogeneidad entre los estudios, no fue posible realizar metaanálisis. CONCLUSIONES: Se emitieron 18 recomendaciones, las cuales servirán como apoyo para la adecuada utilización del MNIO.

Dysferlin quantification in monocytes for rapid screening for dysferlinopathies.

INTRODUCTION: In this study, we determined normal levels of dysferlin expression in CD14+ monocytes by flow cytometry (FC) as a screening tool for dysferlinopathies. METHODS: Monocytes from 183 healthy individuals and 29 patients were immunolabeled, run on an FACScalibur flow cytometer, and analyzed by FlowJo software. RESULTS: The relative quantity of dysferlin was expressed as mean fluorescence intensity (MFI). Performance of this diagnostic test was assessed by calculating likelihood ratios at different MFI cut-off points, which allowed definition of 4 disease classification groups in a simplified algorithm. CONCLUSION: The MFI value may differentiate patients with dysferlinopathy from healthy individuals; it may be a useful marker for screening purposes. Muscle Nerve 54: 1064-1071, 2016.

[Diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy: experience and recommendations for Mexico. Administración del Patrimonio de la Beneficencia Pública. Asociación de Distrofia Muscular de Occidente]. / Diagnóstico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para México.

Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The long-term steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwide on the diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy.

TITLE: Diagnostico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para Mexico.La distrofia muscular de Duchenne es una enfermedad grave, incapacitante y progresiva que afecta a 1 de cada 3.500 recien nacidos varones alrededor del mundo. El diagnostico debera confirmarse mediante pruebas geneticas para identificar la mutacion en el gen DMD, o bien por biopsia muscular e inmunotincion para demostrar la ausencia de distrofina. Aunque actualmente continua siendo una enfermedad incurable, no significa que no tenga tratamiento. Este debe ser multidisciplinario, buscando la funcionalidad del paciente y evitando o corrigiendo las complicaciones, principalmente cardiorrespiratorias y esqueleticas. Se han evaluado e implementado multiples propuestas con la finalidad de mejorar la calidad de vida en estos pacientes. Los esteroides a largo plazo han demostrado importantes beneficios para los pacientes, prolongan la deambulacion, reducen la necesidad de cirugia de columna, mejoran la funcion cardiorrespiratoria, y aumentan la supervivencia y la calidad de vida. En este documento se presentan las recomendaciones con base en la experiencia del grupo de trabajo y de los expertos de ambito mundial sobre el diagnostico y el tratamiento con esteroides para los pacientes con distrofia muscular de Duchenne.

Diagnóstico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para México / Diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy: experience and recommendations for Mexico

La distrofia muscular de Duchenne es una enfermedad grave, incapacitante y progresiva que afecta a 1 de cada 3.500 recién nacidos varones alrededor del mundo. El diagnóstico deberá confirmarse mediante pruebas genéticas para identificar la mutación en el gen DMD, o bien por biopsia muscular e inmunotinción para demostrar la ausencia de distrofina. Aunque actualmente continúa siendo una enfermedad incurable, no significa que no tenga tratamiento. Éste debe ser multidisciplinario, buscando la funcionalidad del paciente y evitando o corrigiendo las complicaciones, principalmente cardiorrespiratorias y esqueléticas. Se han evaluado e implementado múltiples propuestas con la finalidad de mejorar la calidad de vida en estos pacientes. Los esteroides a largo plazo han demostrado importantes beneficios para los pacientes, prolongan la deambulación, reducen la necesidad de cirugía de columna, mejoran la función cardiorrespiratoria, y aumentan la supervivencia y la calidad de vida. En este documento se presentan las recomendaciones con base en la experiencia del grupo de trabajo y de los expertos de ámbito mundial sobre el diagnóstico y el tratamiento con esteroides para los pacientes con distrofia muscular de Duchenne (AU)

Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The longterm steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwide on the diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy (AU)

Immunodetection analysis of muscular dystrophies in Mexico.

INTRODUCTION: The muscular dystrophies (MDs) result from perturbations in the myofibers. These alterations are induced in part by mechanical stress due to membrane cell fragility, disturbances in mechanotransduction pathways, muscle cell physiology, and metabolism. METHODS: We analyzed 290 biopsies of patients with a clinical diagnosis of muscular dystrophy. Using immunofluorescence staining, we searched for primary and secondary deficiencies of 12 different proteins, including membrane, costamere, cytoskeletal, and nuclear proteins. In addition, we analyzed calpain-3 by immunoblot. RESULTS: We identified 212 patients with varying degrees of protein deficiencies, including dystrophin, sarcoglycans, dysferlin, caveolin-3, calpain-3, emerin, and merosin. Moreover, 78 biopsies showed normal expression of all investigated muscle proteins. The frequency rates of protein deficiencies were as follows: 52.36% dystrophinopathies; 18.40% dysferlinopathies; 14.15% sarcoglycanopathies; 11.32% calpainopathies; 1.89% merosinopathies; 1.42% caveolinopathies; and 0.47% emerinopathies. Deficiencies in lamin A/C and telethonin were not detected. CONCLUSION: We have described the frequency of common muscular dystrophies in Mexico.

[Autosomal recessive limb-girdle muscular dystrophy]. / Distrofias musculares de cinturas autosomicas recesivas.

Muscular dystrophies are a heterogeneous group of hereditary diseases characterized by loss of muscle and weakness of non neurogenic origin. They are caused by mutations in one or more genes involved in the formation of muscle cells. The discovery of several proteins in the muscle began with the discovery of dystrophin, 130 years after the clinical description of muscular dystrophy. Currently, due to a better understanding of the biology of normal and diseased muscle, has achieved a classification at the molecular level of different types of muscular dystrophies, according to the protein that is affected. This has been particularly important for limb girdle muscular dystrophies, which present clinical features that can lead to confusion with Duchenne muscular dystrophy. Moreover, in recent years has encouraged the development of therapies in the near future could provide a solution for restoring the function of the muscle fiber.

Distrofias musculares de cinturas autosómicas recesivas / Autosomal recessive limb-girdle muscular dystrophy

Resumen. Las distrofias musculares son un grupo heterogéneo de enfermedades hereditarias, caracterizadas por debilidad y pérdida muscular de origen no neurogénico. Son causadas por mutaciones de uno o más genes involucrados en la formación de las células musculares. El descubrimiento de las diversas proteínas presentes en el músculo comenzó con el descubrimiento de la distrofina, 130 años después de la descripción clínica de la distrofia muscular. Actualmente, debido al mejor conocimiento de la biología del músculo normal y del enfermo, se ha logrado realizar una clasificación molecular de los diferentes tipos de distrofias musculares, de acuerdo con la proteína que se encuentre afectada. Esto ha sido particularmente importante para las distrofias musculares de cinturas, las cuales presentan características clínicas que pueden llevar a confundirlas con la distrofia muscular de Duchenne. Por otro lado, en años recientes se ha favorecido el desarrollo de terapias que en un futuro cercano podrían dar una solución para la restauración de la función de la fibra muscular (AU)

Summary. Muscular dystrophies are a heterogeneous group of hereditary diseases characterized by loss of muscle and weakness of non neurogenic origin. They are caused by mutations in one or more genes involved in the formation of muscle cells. The discovery of several proteins in the muscle began with the discovery of dystrophin, 130 years after the clinical description of muscular dystrophy. Currently, due to a better understanding of the biology of normal and diseased muscle, has achieved a classification at the molecular level of different types of muscular dystrophies, according to the protein that is affected. This has been particularly important for limb girdle muscular dystrophies, which present clinical features that can lead to confusion with Duchenne muscular dystrophy. Moreover, in recent years has encouraged the development of therapies in the near future could provide a solution for restoring the function of the muscle fiber (AU)