Expansion of the Phenotypic Spectrum of TNRC6B-Related Neurodevelopmental Disorder in a Three-Generation Family with...

Background:TNRC6B encodes a core effector of the RNA-induced silencing complex and is essential for miRNA-mediated gene silencing. Pathogenic variants in TNRC6B have recently been associated with a neurodevelopmental disorder characterised by developmental delay, intellectual disability, and behavioural difficulties. Methods: We report a three-generation family with a 22q13.1 deletion encompassing only exons 2-23 of TNRC6B. Clinical data were collected from medical records and family interviews, and the findings were compared with those of published cohorts. Results: Affected individuals presented with developmental delay, speech and language impairment, autism spectrum disorder, ADHD, oppositional defiant disorder, craniosynostosis, joint laxity, clinodactyly, and cardiac valve anomalies. The father and paternal grandmother had learning difficulties and neurobehavioral features, while the proband exhibited a more severe phenotype. Conclusions: This report expands the phenotypic spectrum of TNRC6B-related neurodevelopmental disorder, highlighting craniosynostosis, joint and connective tissue features, and cardiac involvement. Our findings also underscore variable expressivity across generations and emphasise the relevance of both copy-number and sequence variants in TNRC6B in patients with neurodevelopmental disorders.