Two Japanese Cases Highlighting Structural and Phenotypic Overlap in AGO1- and AGO2-Related Neurodevelopmental Disorders.
Munetsugu Hara, Nobuhiko Okamoto, Yukihiro Kitai et al.
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Case in brief
Two unrelated Japanese individuals presented with global developmental delay, hypotonia, midface hypoplasia, thin upper lip, elongated facial shape, and reduced cerebral white matter volume. Genetic analysis revealed de novo variants in AGO1 and AGO2, affecting residues at the L1-PAZ boundary, which are crucial for RNA engagement. These findings align with known phenotypes associated with AGO1 and AGO2-related disorders.
Diagnostic / clinical pearl
Clinicians should consider AGO1 and AGO2 variants in patients with unexplained neurodevelopmental disorders, particularly when presented with characteristic craniofacial features and developmental delays.
Why it matters
This case underscores the importance of recognizing structural and phenotypic overlaps in neurodevelopmental disorders, which may enhance diagnostic accuracy and patient management.