Expanding the Phenotypic Spectrum of -Related Intellectual Disability: Description of Two Portuguese Patients and Review of the Literature.

Introduction: Pathogenic variants in have been associated with a neurodevelopmental disorder mainly characterized by intellectual disability, severe language impairment, and motor developmental delay. Since its first description in 2016, only 15 patients have been described in the literature.

Methods: Here, we report 2 additional unrelated Portuguese children presenting intellectual disability and motor delay in whom de novo nonsense pathogenic variants in have been identified by next-generation sequencing analysis.

Results: In patient 1, the variant c.2827C>T, p.(Arg943*) was detected, whereas patient 2 carried the variant c.6667C>T, p.(Arg2223*). Interestingly, patient 1 presented with a rapid growth of the occipitofrontal diameter in the first months of life due to external hydrocephalus, a feature that, as far as we know, has never been reported in patients with pathogenic variants.

Conclusion: This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by comparing the clinical features of our patients with previously reported affected individuals.