• Pure 16q12.2 duplications are extremely rare and clinically relevant. • Schizophrenia was observed in a young adult with de novo 16q12.2 duplication. • Neurodevelopmental phenotype includes cognitive impairment and severe dyspraxia. • Marked intolerance to antipsychotics, including catatonia at low doses. • 16q12.2 may represent a susceptibility locus for schizophrenia and drug response. Copy number variations (CNVs) are increasingly recognized as important contributors to neurodevelopmental and psychiatric disorders. Duplications involving the long arm of chromosome 16 (16q) are rare and associated with heterogeneous phenotypes, including developmental delay, cognitive impairment, and behavioral disturbances. Pure duplications of the proximal 16q region, particularly 16q12.2, are exceedingly rare, and their psychiatric relevance remains largely unexplored. We report the case of a 25-year-old man with schizophrenia associated with a de novo pure duplication of chromosome 16q12.2, initially identified in childhood during evaluation for learning disabilities and dyspraxia. His neurodevelopmental history was characterized by global developmental delay, cognitive impairment, severe dyspraxia, learning disabilities, and persistent neurological signs. Psychotic symptoms emerged insidiously in early adulthood, including persecutory delusions, auditory hallucinations, disorganization, and subsequent catatonic features. The clinical course was marked by pronounced intolerance to multiple antipsychotic treatments, with severe extrapyramidal symptoms and catatonia occurring even at low doses. Extensive neurological, immunological, and paraclinical investigations yielded no contributory findings. Symptom remission was ultimately achieved with low-dose olanzapine, although relapses occurred in the context of cannabis use. This case expands the phenotypic spectrum associated with pure 16q12.2 duplications and suggests that this genomic region may constitute a susceptibility locus for schizophrenia and antipsychotic intolerance. Further case reports, cohort studies, and functional investigations are needed to clarify the underlying pathogenic mechanisms and clinical implications of 16q12.2 duplications.
Jeannin et al. (Wed,) studied this question.