ReNU syndrome –⁠ a newly described prevalent neurodevelopmental disorder: first case in the Czech Republic

Overview

Slabá K, Pokorná P, Koželková K, Hloušková E, Jugas R, Kubátová J, Demlová R, Danhofer P, Jabandžiev P, Svatoňová T, Slabý O. Renu syndrome – a newly described prevalent neurodevelopmental disorder: first case in Czech republic

We present the case of a 5 and half year-old boy with severe global developmental delay, hypotonia, severe growth failure, failure to thrive, craniofacial dysmorphism, and other difficulties, who was diagnosed by whole genome sequencing (WGs). the diagnosis was carried out within the czech national project BabyFox. a pathogenic variant in the RNU4-2 gene was identified in the patient, which has been associated with the prevalent disorder known as rnu4-2 neurodevelopmental delay syndrome, also known as renu syndrome since 2024. although it is a newly described diseases, renu syndrome is one of the most prevalent monogenic neurodevelopmental disorder, with pathogenic variants in the rnu4-2 gene estimated to cause approximately 0.4% of all neurodevelopmental disorders. this gene does not encode a protein but rather a small nuclear rna u4, which means its sequence is not captured by standard whole-exome sequencing or targeted sequencing panels. as a result, its significance remained overlooked until 2024. The case of renu syndrome highlights the importance of whole-genome sequencing, which covers non-coding regions of the genome, in the diagnosis of rare genetic disorders. it also demonstrates how the implementation of modern genomic methods can help end the diagnostic odyssey for patients with previously unexplained neurodevelopmental disorders.

Keywords:

neurodevelopmental disorder – diagnostic odyssey – whole-genome sequencing – non-coding variant – renu syndrome – RNU4-2 gene.