Background: Neonatal cardiomyopathies are rare diseases of the heart muscle associated with cardiac dysfunction. There are different presentations, such as hypertrophic, dilated, or restrictive forms, as well as noncompaction and arrhythmogenic right ventricular cardiomyopathies. Dilated cardiomyopathy is characterized by cardiac dilatation and reduced systolic function. Neonatal onset of dilated cardiomyopathy can have a rapid progression to cardiac decompensation and death unless the patient undergoes heart transplantation.Myocarditis is responsible for the majority of cases of dilated cardiomyopathy, but it can be a consequence of different pathologies (ischemia, arrhythmias, endocrine, metabolic, systemic, autoimmune disorders, toxic…), so differential diagnosis is quite broad. Genetic forms of dilated cardiomyopathy include different modes of inheritance, but we present a novel mutation in the ribosomal protein large 3-like (RPL3L) gene. RPL3L genes encode the 60S ribosomal protein, which is specifically expressed in cardiac and skeletal muscle.Case presentation summary: A previously healthy full-term 15-day-old male neonate with an unremarkable antenatal and perinatal history (non-consanguineous family with healthy parents, originated from Colombia), was admitted to our hospital for feeding difficulty, irritability without fever, in the last two days.Examination revealed tachycardia with a gallop rhythm, tachypnea, and irritability. Blood workup showed lactic acidosis (8.1 mmol/l), high heart failure biomarker levels (Troponin I 370 ng/ml, NT-ProBNP 63.642 pg/ml), and the rest of the laboratory tests were normal and inconclusive for infection. His electrocardiogram showed sinus tachycardia, with biatrial enlargement and nonspecific repolarization abnormalities. Echocardiogram showed a normal structural heart but with a marked left ventricular dilatation (25mm) with depressed fractional shortening 18% and mild mitral regurgitation.Patient was admitted to the NICU for further management, his heart failure worsened while remaining intubated and on inotropic support, and on day 14 of illness, he was placed on extracorporeal membrane oxygenation (ECMO), and on day 23, the implantation of the Berlin Heart Excor® ventricular assist device was performed. On day 24, he required a heart transplantation, but unfortunately died at the age of 2 months. Genetic analysis revealed two heterozygous variants in RPL3L gene, c.922G>A, (p.Asp308Asn) inherited from his mother, and c.76C>T (p.Arg26Trp) inherited from his father. (picture)Learning points discussion:1.- The ribosomal protein large 3-like (RPL3L) gene plays a role in cardiomyocyte growth and function. The involvement of ribosomal factors in the pathogenesis of dilated cardiomyopathy possibly reveals a novel disease-associated mechanism.2.- Bi-allelic missense variants in RPL3L caused a severe dilated cardiomyopathy in the neonatal period. Early genetic diagnosis can inform management decisions and family counseling.3.- RPL3L is a newer and likely pathogenic gene associated with a severe form of early-onset dilated cardiomyopathy with poor prognosis necessitating heart transplantation, but further research is needed to elucidate the pathogenic mechanisms of RPL3L-related cardiomyopathy
