agnostically challenging condition in which hypokinetic–rigid features most commonly result from defects in neurotransmitter biosynthesis or metabolism rather than the primary dopaminergic neurodegeneration observed in adults. Impairments in dopamine and serotonin pathways lead to monoamine deficiency, clinically manifesting as dystonia, oculogyric crises, and bradykinesia [1]. This condition is broadly classified into developmental and degenerative forms. The former results from impaired maturation of dopaminergic circuitry, whereas the latter is characterized by progressive nigrostriatal degeneration and may occur as part of complex multisystem neurodevelopmental disorders WW domain- containing oxidoreductase (WWOX) is a key regulator of neural development, synaptic homeostasis, and cortical organization. However, its role in monoamine pathways remains not well defined. Experimental studies suggest that WWOX modulates the vulnerability of dopaminergic neurons through interactions with JNK1 (stress- related kinase), particularly, which is involved in neurodegenerative signaling cascades [2]. Furthermore, genome- wide association studies have identified variants at the WWOX locus as genetic modifiers associated with accelerated progression to dementia in Parkinson's disease, suggesting a modulatory role in dopaminergic resilience rather than primary neurodegeneration Pathogenic WWOX variants are well- established causes of severe neurodevelopmental disorders including SCAR12 and WOREE (WWOX- related epileptic encephalopathy). However, a parkinsonian phenotype has not been reported in humans to date. Here, we describe the first case of neonatal–infantile parkinsonism associated with a pathogenic WWOX variant, clinically mimicking a primary monoamine neurotransmitter synthesis defect.
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