A Novel ZMIZ1 Pathogenic Variant in a Chinese Girl with Neurodevelopmental Disorder and Review of the Literature

Pathogenic variants in the ZMIZ1 gene have been associated with neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA). To date, only five reports have identified ZMIZ1 mutations in patients with neuropsychiatric alterations. Here we described a Chinese pediatric patient with intellectual disability (ID), early and fast puberty, growth restriction, and mild facial dysmorphisms, who had a novel pathogenic variant in ZMIZ1 (NM_020338.4:c.40C > T:p.Arg14*). Meanwhile, we demonstrated the molecular and phenotypic features of individuals carrying the ZMIZ1 heterozygous variants through a comprehensive literature review. ID (100%), facial dysmorphism (90.91%), speech developmental delay (90.48%), abnormal behaviors (85%), motor developmental delay (78.95%), and eye anomalies (71.43%) were identified as the most represented clinical features. Our findings present the second Chinese case of NEDDFSA and report a novel heterozygous ZMIZ1 mutation which expands the variant spectrum of the ZMIZ1 gene. Furthermore, we suggest that the penetrance of NEDDFSA is almost complete but with highly variable expressivity.