Expanding the Phenotypic Spectrum of HNRNPU-Related Disorder, Documenting the First Familial Presentation and...

HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) is caused by pathogenic and likely pathogenic variants in HNRNPU. With increasing accessibility to advanced genetic investigations, children presenting with developmental delay and intellectual disability will often undergo genomic testing; hence, the number of patients found to be affected by HNRNPU-NDD is increasing. We document a cohort of 17 previously unpublished patients with HNRNPU variants, including the first familial case, building on those previously published by our group. A comprehensive literature review was performed, identifying previously published patients and phenotypes for comparison. Eighty-four patients have been published in previous studies with pathogenic variants in HNRNPU with the following phenotypes: Global developmental delay, moderate to severe intellectual disability, early-onset seizures, and dysmorphic features. In addition to these phenotypes previously described, we have recognized ophthalmic abnormalities, cardiac abnormalities, and short stature in our cohort. We provide information on patients with a milder phenotype, enhancing our knowledge of phenotypic variability in HNRNPU-NDD.