Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy

ABSTRACT Background: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limb-girdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. Objective: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. Methods: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. Results: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. Conclusions: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.

Avances en la fisiopatologia y tratamiento de la hipertensión arterial pulmonar postoperatoria grave / Advances in the pathophysiology and treatment of postoperative pulmonary hypertension

Pulmonary hypertension is a condition frequently seen and associated to many cardiovascular diseases and can become a hemodynamic complication in postoperative period. This can require the integral management in the intensive care room. In the last years we have many new concepts about the pathophysiology of this condition and new therapeutic options. In this paper we review the current strategies for the management of this condition.

Uso del levosimendan previo a la cirugía cardíaca, en pacientes con mala función ventricular / Usefulness of levosimendan in patients with ventricular dysfunction before surgery

El propósito de este trabajo fue observar los resultados hemodinámicos inmediatos (primeras 24 hs) en pacientes con mala función ventricular (< 40%), considerados de alto riesgo quirúrgico, en los cuales 24 a 48 hs antes de la cirugía recibían una infusión por 24 hs con levosimendan. Se incluyeron 4 pacientes de sexo masculino con edad promedio de 55.50 (+ 7.93 años) con una fracción de eyección del ventrículo izquierdo de 31 (+ 5.47%), 2 de ellos sometidos a cambio valvular, otro a revascularización miocárdica y el cuarto se sometió a procedimiento combinado (revascularización + cambio valvular). El comportamiento de los parámetros hemodinámicos estuvo estable, sin necesidad de altas dosis de los inotrópicos y vasopresores clásicos en el postoperatorio. Conclusión: El levosimendan podría ser un inotrópico de gran aplicación en este grupo de pacientes debido a su novedoso mecanismo de acción y a sus sostenidos efectos hemodinámicos luego de terminada su infusión.

The purpose of this work was to observe the hemodynamic stability on the first 24 hours in 4 patients with ventricular dysfunction (Ejected Fraction < 40 %), considered of high surgical risk, in which 24 at 48 hr before the surgery received an infusion of Levosimendan for 24 hours. This 4 patients was male, with age 55.5 ± 7.9 years old, a left ventricle ejection of fraction (LVEF) of 31 ± 5.47%; Two of them was underwent to valve replacement, another one to coronary artery bypass graft and the last one patient underwent combined procedure (coronary artery bypass graft surgery and valve replacement). The behavior of the hemodynamic parameters was stable, without necessity of uses high dose of the inotropics and classic vasopresores in the postoperative. Conclusion: the Levosimendan could be an inotropic of great application in this group of patient due to its novel action mechanism and to its sustained hemodynamic effects after having finished its infusion.

Avances en el tratamiento médico de la insuficiencia cardiaca / Advances in the medical treatment of heart failure

La insuficiencia cardiaca, es una de las entidades con mayor incidencia en los últimos años. Debido al avance en diversas áreas de la práctica cardiológica, cada vez se presenta con mayor frecuencia, lo que ha obligado a un mayor conocimiento de sus mecanismos de progresión y a la investigación de fármacos con la finalidad de aliviar la sintomatología y con ello mejorar la clase funcional de estos enfermos. Desde luego, el tratamiento con medidas dietéticas, tales como baja ingesta de sodio y restricción hídrica se han mantenido en uso durante muchos años, así como diuréticos y digitálicos. Sin embargo, han surgido nuevas alternativas de tratamiento médico, las cuales se analizan en el presente trabajo y que en los años por venir, sin duda serán perfeccionadas e incorporadas al armamentario terapéutico.