Cardiological Manifestations in Males and Females Affected by NAA10‐Related Disease

We report a family with two affected brothers presenting hypertrophic cardiomyopathy, prolonged QT interval, and intellectual disability who, after a dozen years of inconclusive genetic testing, were found to share a previously undescribed variant c.549delA (p.Gly184Alafs*67) in the X-linked NAA10 gene. Their mother was heterozygous for the variant and had a long history of unexplained cardiac arrhythmia. NAA10 (N-alpha-acetyltransferase 10) is a component of the N-terminal acetyltransferase A complex (also called the NatA complex) necessary for N-alpha-acetylation, among the most common post-translational protein modifications in eukaryotic cells. Deleterious variants in the X-linked NAA10 gene cause a wide spectrum of clinical features, recently merged under the umbrella term of NAA10-related disease, mainly featuring intellectual disability, seizures, visual and cardiac abnormalities. Congenital heart defects and cardiac dysfunction/arrhythmias emerged as a very common manifestations of the disease both in males and females described in the medical literature. While atrial and ventricular septal defects dominated at pediatric age in both sexes, hypertrophic cardiomyopathy, and prolonged QT were observed in adult males and females, respectively. Our observations may help in the early recognition of NAA10-related disease based on previously underrecognized cardiac features, especially in females with unexplained arrhythmias and/or prolonged QT, and guide personalized management of this neglected condition.