PUS7 Deficiency: Phenotypical Expansion of PUS7 ‐Related Neurodevelopmental Disorders

Pathogenic variants in PUS7, encoding pseudouridine synthase 7, cause a rare neurodevelopmental disorder marked by intellectual disability, microcephaly, short stature, and behavioral disturbances. Since the first report in 2018, only 16 patients have been described. We report a novel case with a homozygous pathogenic PUS7 variant and present an updated review of all cases published between 2018 and 2025. Across 17 cases, the most frequent features were moderate/severe intellectual disability, delayed/absent speech, aggressive behavior, microcephaly, mild facial dysmorphisms, motor delay, and short stature. These features are common but non-specific, with the exception of aggressiveness that manifests at a very early age. Less common but more peculiar findings included sensorineural hearing loss, autistic traits, self-injurious behavior, and motor stereotypies. The combination of core features with these more specific symptoms should prompt suspicion of a PUS7-related disorder. We recommend looking for PUS7 pathological variants when performing whole exome sequencing in children with this constellation of neurodevelopmental and behavioral signs.