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EV0652

Early-onset familial psychotic disorder in an adolescent and segregation analysis of selected candidate gene polymorphisms in a multiply affected family

FAMILIAL PSYCHOTIC DISORDER WITH EARLY ONSET IN AN ADOLESCENT AND SEGREGATION ANALYSIS OF SELECTED CANDIDATE GENE POLYMORPHISMS ACROSS A MULTIPLEX FAMILY

In this family with a high burden of psychotic illness, four selected candidate gene polymorphisms did not show consistent segregation with illness.

The aim of the study was to describe the clinical course of an adolescent with early-onset psychosis and examine the intrafamilial distribution of selected candidate gene polymorphisms. Clinical and genetic data were collected from six individuals, comprising four affected and two unaffected family members; all individuals were genotyped for ZNF804A (rs1344706), CACNA1C (rs4765913), NOTCH4 (rs367398), and NNMT (rs694539), and genotype distributions were assessed for co-segregation with clinical status. The index case was a 15-year-old adolescent diagnosed with schizoaffective disorder, presenting with persecutory delusions, auditory and visual hallucinations, and disorganized thinking, with a history of suicidal behavior and two psychiatric hospitalizations. The family pedigree included schizophrenia in the mother, schizoaffective disorder in the father, and schizophrenia in the older brother, while the younger brother and maternal aunt were unaffected. Despite the strong familial burden of psychotic illness, none of the polymorphisms examined showed consistent segregation with illness; risk alleles were also detected in some unaffected relatives, while some affected individuals did not carry the same alleles. The distribution within the family exhibited a heterogeneous, non-Mendelian pattern. The authors emphasize that these findings support the polygenic and complex nature of psychotic disorders and highlight the need for broader genomic approaches, such as copy number variation (CNV) analysis and whole-exome sequencing, in familial cases.

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