Dilated aorta in CNOT3-related neurodevelopmental disorder: ‘expanding’ the phenotype

Abstract

Introduction Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child’s development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype–phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management. Methods In this study, we report a case of a patient with CNOT3-related NDD who presented with progressive aortic dilatation, a feature not reported previously. Results Our patient presented with intellectual disorder, dysmorphic facial features, and cardiac anomalies, notably progressive aortic dilatation – a novel finding in CNOT3-related NDD. Genetic testing identified a de novo 6.3 kbp intragenic deletion in CNOT3, providing a possible genetic basis for her condition. Conclusion This study presents the first case of CNOT3-related NDD in Southeast Asia, expanding the phenotype to include progressive aortic dilatation and suggesting merit in cardiac surveillance of patients with CNOT3-related NDD. It also emphasizes the importance of genetic testing in diagnosing complex NDD cases as well as reanalysis of ‘negative’ cases using advanced sequencing technologies to uncover potential hidden genetic etiologies in undiagnosed NDDs.