Duplication in the pogz gene and psychiatric manifestations in twin brothers with white sutton syndrome

White Sutton Syndrome (WSS) is a rare neurodevelopmental disorder resulting from mutations in the POGZ gene. The clinical presentation is often non-specific. Here we report one such case detected to have variants suggestive of WSS. Twin brothers, 24-year-old, the youngest of 5 siblings, presented with symptoms of body dysmorphophobia, and obsessions, followed by a gradual decline in social functioning, over many years. Early development had been unremarkable, but their social interactions began to gradually decline after the age of 9-10 years, and they became withdrawn. Mental status examination of one twin revealed reduced psychomotor activity, and apathetic affect. The other twin also had obsessive ruminations, mental compulsions, and depressed affect, but with fair insight. The MRI-Brain of one of them indicated bilateral hyperintensities in the periventricular frontal region. The same twin also had brisk deep tendon reflexes and refractive error. A working diagnosis of Obsessive Compulsive disorder with possibility of prodrome of psychosis was considered. Both were treated with Amisulpride, SSRI, and behavioural interventions, with some improvement in obsessive compulsive symptoms, as well as social interaction. Multiple second degree relatives had been diagnosed to have opioid dependence syndrome, completed suicide, depressive disorder, and obsessive-compulsive disorder. Whole exome sequencing (WES) was requested considering similar illnesses, vague presentation, and considerable family loading. Whole exome sequencing revealed a hemizygous X Linked dominant variant (c.935A>G (p.Asn312Ser) for intellectual development disorder-41, GDI-1 gene (OMIM#300849), and heterozygous copy-number variant for an autosomal dominant variant for WSS on Chromosome 1, POGZ gene (chr1:g.(?_151364543)_(151430841_?)dup (OMIM#616364). The GDI-1 mutation is usually reported in intellectual developmental disorder. Individuals carrying mutations in the POGZ gene have varied phenotypes, from being only mildly affected, to learning and attention difficulties, and severe dysmorphic features. These twins had some temperamental traits, followed by progressively severe symptoms and social withdrawal. Our cases were detected to have a duplication of POGZ which although commonly reported in literature, the clinical significance remains inconsequential. Obsessive compulsive symptoms however have been rarely reported in literature in individuals with likely pathogenic variants of POGZ. Lack of genetic testing of parents limits our ability to comment upon de-novo versus heterozygous inheritance. Both parents were in their late 30s when the twins were born. The mother was the last born of her five siblings herself, and the twin pair were the last born. This could increase the risk of de-novo mutations This case highlights that variations in genes linked to ID syndromes may show pleiotropy and thus variable phenotypes, including psychological symptoms.