Genotype-Phenotype Correlation and Psychiatric Manifestations in a Case of Phelan-McDermid Syndrome With 22q13.33...

Phelan-McDermid syndrome (PMS) (OMIM: 606232) is a rare genetic disorder usually caused by deletions in the 22q13.3 region, often affecting the SHANK3 gene, which is essential for synaptic function and neurodevelopment. PMS is clinically heterogeneous, presenting with intellectual disability, language deficits, hypotonia, and psychiatric conditions such as autism spectrum disorder and bipolar disorder. We present the case of a 29-year-old woman with intellectual disability, language impairment, and bipolar disorder. She was initially diagnosed with a ring chromosome 22, and subsequent microarray analysis revealed a pathogenic deletion involving SHANK3. Clinically, she displayed affective instability, recurrent psychotic episodes, multiple psychiatric hospitalizations, facial dysmorphisms, scoliosis, and an increased pain threshold. This case illustrates the importance of integrating genetic and psychiatric evaluations in patients with intellectual disability who present with early-onset psychiatric symptoms. Timely recognition of psychiatric manifestations in PMS has direct clinical implications, as early interventions may improve outcomes. Furthermore, the coexistence of a ring chromosome 22 and a 22q13.3 microdeletion highlights the complexity of genotype-phenotype correlations in PMS and suggests that genes beyond SHANK3 may influence neurodevelopmental and psychiatric features.