Occupational hazards in hip and knee adult reconstruction surgery : a systematic review of physical and psychological stressors.

-related neurodevelopmental disorder (Protein Phosphatase 1 Regulatory subunit 21; Online Mendelian Inheritance in Man [OMIM] #619383) is an autosomal-recessive encephalopathy marked by severe intellectual disability (ID), hypotonia, a coarse craniofacial gestalt, and structural brain abnormalities [–]. variants were first implicated in ID within a large cohort of individuals with cognitive impairment described in 2017, and published cases remain few (≈ two dozen by 2025) [–, –]. The disorder illustrates the diagnostic yield of next-generation sequencing, particularly whole-exome sequencing, in consanguineous populations [, , , –]. Beyond rarity, its significance lies in mechanistic insight: converging evidence implicates early endosomal trafficking and putative endosome-coupled local messenger RNA (mRNA) translation in neurons [, , , , ]. Accordingly, , , and have been proposed as a shared “FERRY complex” disease class with overlapping neurodevelopmental features. Comparative delineation of those disease entities remains limited and recent reviews have outlined open questions regarding this putative disease spectrum [, , ]. Key gaps include incomplete adult phenotyping, limited genotype–phenotype correlation, uncertain links between FERRY dysfunction and clinical manifestations, and the lack of targeted therapeutic approaches. PPP1R21 protein forms the structural backbone of the five-subunit FERRY complex and binds Rab5-GTP on early endosomes. The complex is proposed to couple early endosomal transport with the shuttling of specific mRNAs to enable local translation, particularly in neurons. This positioning provides a mechanistic link between endosomal trafficking and neurodevelopmental phenotypes in deficiency [, –]. This review integrates the clinical, neuroimaging, and molecular spectrum of -related neurodevelopmental disorders with current understanding of its underlying molecular mechanisms, providing pragmatic diagnostic and management guidance and outlining priorities for future translational studies.