Síndrome de Andersen Tawil en una embarazada con alto riesgo de muerte súbita. Reporte de caso / Andersen Tawil syndrome in a pregnant woman at high risk of sudden death

Resumen ANTECEDENTES: El síndrome de Andersen Tawil es una canalopatía multisistémica genética, muy rara, sin alteración cardiaca estructural, heredada de manera autosómica dominante y causada por mutación en el gen KCNJ2. Este síndrome se caracteriza por una triada de parálisis muscular periódica, cambios en el electrocardiograma y estructurales corporales. El rasgo distintivo es la taquicardia ventricular bidireccional, las contracciones ventriculares prematuras y raramente taquicardia polimórfica tipo torsade de pointes. En la actualidad se carece de guías para el peri y postparto y para la prevención de arritmias. CASO CLÍNICO: Paciente de 21 años, embarazada, con síndrome de Andersen Tawil diagnosticado a esta edad, con base en los antecedentes de síncope de repetición y debilidad en las extremidades desde los 11 años. Recibía tratamiento con un beta-bloqueador y un desfibrilador automático implantable. La ecocardiografía fetal a las 23 y 33 semanas de gestación reportó una comunicación interventricular apical de 1.6 mm. A las 39 semanas de embarazo se practicó una cesárea electiva, con evolución posoperatoria satisfactoria. El estudio molecular dirigido al recién nacido descartó el síndrome de Andersen Tawil congénito. CONCLUSIÓN: En pacientes con síndromes de arritmia congénita, el embarazo puede ser seguro siempre y cuando un grupo de especialistas esté pendiente para tomar decisiones de atención y tratamiento durante todo el proceso del embarazo y puerperio.

Abstract BACKGROUND: Andersen Tawil syndrome is a very rare genetic multisystemic channelopathy without structural cardiac alteration, inherited in an autosomal dominant manner and caused by mutation in the KCNJ2 gene. This syndrome is characterised by a triad of periodic muscle paralysis, electrocardiogram and body structural changes. The hallmark is bidirectional ventricular tachycardia, premature ventricular contractions and rarely polymorphic torsade de pointes tachycardia. Currently there is a lack of guidelines for peri- and postpartum and arrhythmia prevention. CLINICAL CASE: 21-year-old pregnant patient with Andersen-Tawil syndrome diagnosed at this age, based on a history of repeated syncope and weakness in the extremities since the age of 11. She was being treated with a beta-blocker and an implantable cardioverter defibrillator. Fetal echocardiography at 23 and 33 weeks gestation reported an apical ventricular septal defect of 1.6 mm. Elective caesarean section was performed at 39 weeks of pregnancy, with satisfactory postoperative evolution. Molecular study of the newborn ruled out congenital Andersen-Tawil syndrome. CONCLUSION: In patients with congenital arrhythmia syndromes, pregnancy can be safe as long as it is managed by a group of experts to make decisions and optimise care throughout the pregnancy and postpartum period.

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.

Síndrome de Andersen-Tawil: una revisión del diagnóstico genético y clínico con énfasis en sus manifestaciones cardíacas / Andersen-Tawil syndrome: A review of its clinical and genetic diagnosis with emphasis on cardiac manifestations

El síndrome de Andersen-Tawil resulta de la alteración de canales de potasio, se hereda de forma autosómica dominante y se cataloga como el tipo 7 de los síndromes de QT largo congénitos. El gen afectado es el KCNJ2, el cual codifica la proteína Kir2.1 que forma el canal de potasio rectificador interno («inward rectifier¼). Este canal interviene en la estabilización del potencial de membrana en reposo y controla la duración del potencial de acción en el sistema musculoesquelético y cardíaco. En miocitos ventriculares, es un componente responsable de la rectificación de la corriente de potasio en la fase 3 del potencial de acción. Debido a que Kir2.1 está presente en el sistema musculoesquelético, corazón y cerebro, las alteraciones de esta proteína dan origen a las principales características del síndrome: parálisis flácida, arritmias ventriculares y alteraciones leves a moderadas en el desarrollo del esqueleto, especialmente en manos y pies. En la presente revisión se aborda esta enfermedad desde el punto de vista del diagnóstico clínico y molecular con énfasis en sus manifestaciones cardíacas.

The Andersen-Tawil syndrome is a cardiac ion channel disease that is inherited in an autosomal dominant way and is classified as type 7 of the congenital long QT syndromes. Affected gene is KCNJ2, which forms the inward rectifier potassium channel designated Kir2.1. This protein is involved in stabilizing the resting membrane potential and controls the duration of the action potential in skeletal muscle and heart. It also participates in the terminal repolarization phase of the action potential in ventricular myocytes and is a major component responsible for the correction in the potassium current during phase 3 of the action potential repolarization. Kir 2.1 channel has a predominant role in skeletal muscle, heart and brain. Alterations in this channel produce flaccid paralysis, arrhythmias, impaired skeletal development primarily in extremities and facial area. In this review we address the disease from the point of view of clinical and molecular diagnosis with emphasis on cardiac manifestations.

Ventricular Tachyarrhythmias in a Patient with Andersen-Tawil Syndrome

Andersen-Tawil syndrome (ATS), a rare autosomal dominant disorder, is characterized by periodic paralysis, dysmorphic features and cardiac arrhythmias. This syndrome is caused by mutations of KCNJ2 gene, which encodes inward rectifying potassium channel. Here, we report an 18-year-old girl who was presented with life-threatening cardiac arrhythmia and acute respiratory distress. She was diagnosed with ATS, based on dysmorphic features, ventricular arrhythmia, and periodic paralysis. This is the first case to be reported in Korea who experienced a fatal cardiac arrest and respiratory failure caused by ATS.

Andersen-Tawil Syndrome – Periodic Paralysis with Dysmorphism.

Andersen-Tawil syndrome is a rare type of channelopathy characterized by the presence of periodic paralysis, cardiac arrhythmia (prolonged QT interval or ventricular arrhythmia) and distinct dysmorphic abnormalities. It is a type of potassium channelopathy that occurs sporadically or by autosomal dominant inheritance. We report a 14 year old boy with Andersen-Tawil syndrome.