ISSN: 0034-8376
eISSN: 2564-8896






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



David R. Barrón-Díaz, Department of Electrocardiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico; Social Service Program, Faculty of Medicine, Universidad Autónoma de Coahuila, Unidad Torreón, Coah., Mexico
Armando Totomoch-Serra, PhD Program in Medical Sciences, Universidad de La Frontera, Temuco, Chile; Department of Genetics and Molecular Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
Rosa E. Escobar-Cedillo, Electrodiagnosis and Muscular Dystrophy Service, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
Alan García-Gutierrez, Department of Electrocardiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico;
Álvaro E. Reyes-Quintero, Department of Electrocardiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico
Sergio E. Villegas Davirán, Electrodiagnosis and Muscular Dystrophy Service, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
Concepción B. Ibarra-Miramón, Department of Evaluation and Treatment, Centro Nacional Modelo de Atención, Investigación y Capacitación para la Rehabilitación e Integración Educativa "Gaby Brimmer", Mexico City, Mexico
Manlio F. Márquez, Department of Electrophysiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico


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 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: Extracardiac 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.



Keywords: Andersen-Tawil syndrome. Phenotypic variability. KCNJ2 pathogenic variants. Long-exercise electrophysiological test. Periodic paralysis.