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Case Reports
. 2025 Jan;107(1):104-112.
doi: 10.1111/cge.14628. Epub 2024 Oct 21.

RNU4-2-Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt

Jessica Rosenblum  1   2 , Diane Beysen  3 , Anna C Jansen  2   3 , Marjan De Rademaeker  1 , Edwin Reyniers  1 , Katrien Janssens  1 , Marije Meuwissen  1
Affiliations
Case Reports

RNU4-2-Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt

Jessica Rosenblum et al. Clin Genet. 2025 Jan.

Abstract

De novo heterozygous variants in RNU4-2, a component of the major spliceosome, were recently found to cause a novel neurodevelopmental disorder. Preliminary evidence suggests that this newly discovered syndrome is one of the most common monogenic causes of neurodevelopmental disorders. It is characterised by developmental delay and intellectual disability, microcephaly, short stature and hypotonia. However, much remains to be elucidated regarding the phenotype of the affected individuals. We report on four novel individuals affected by the condition, two of which were identified following targeted sequencing based solely on the facial features that were similar to those of the first patient we identified. This strongly suggests that this syndrome entails a recognisable morphological phenotype, which is particularly relevant for resource-limited regions where whole genome sequencing is not readily available, and in view of retro-active selection/prioritisation of individuals with hitherto negative genetic testing.

Keywords: RNU4‐2; deep phenotyping; dysmorphology; neurodevelopmental disorder; non‐coding genome.

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References

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