Psychosis and autism without functional regression in a patient with Kleefstra syndrome.

This study reports on a 35-year-old man with Kleefstra syndrome (a rare genetic condition) who developed autism and schizophrenia. Unlike other cases, he didn't experience a decline in his abilities when the schizophrenia developed. His psychotic symptoms completely improved with medication (zuclopenthixol), which is the first time this treatment success has been reported in someone with Kleefstra syndrome.

This case report describes a 35-year-old male with Kleefstra syndrome who developed autism spectrum disorder and schizophrenia with manic features, but notably without functional regression. Kleefstra syndrome is a rare genetic disorder caused by EHMT1 gene haploinsufficiency, typically associated with intellectual disability, dysmorphic features, and neuropsychiatric symptoms including autism and psychosis. The patient's psychotic symptoms achieved complete remission with zuclopenthixol treatment, representing the first documented successful treatment of psychosis in Kleefstra syndrome. This case challenges the assumption that functional regression necessarily accompanies psychotic presentations in this population and provides insight into the psychiatric phenomenology of this rare genetic condition.

Suggests zuclopenthixol may be effective for psychotic symptoms in Kleefstra syndrome. Indicates that functional regression is not inevitable with psychotic presentations. Emphasizes need for comprehensive psychiatric assessment in individuals with this genetic syndrome, particularly monitoring for both autism and psychotic features.

Single case report with no control group or systematic comparison. Limited generalizability due to the rarity of Kleefstra syndrome. No long-term follow-up data provided for treatment response or clinical course.

Kleefstra syndrome is a rare genetic disorder caused by haploinsufficiency of the euchromatic histone lysine methyltransferase 1 (EHMT1) gene. It is characterized by a variety of dysmorphic features, comorbid medical issues, and developmental delays/intellectual disability. Neuropsychiatric symptoms may also occur, including autistic features and psychosis, and are often accompanied by functional regression. However, the phenomenology of psychotic symptoms in this syndrome has not been well described in the literature.

As such, in this brief report, we review the literature with respect to the occurrence of psychosis in Kleefstra syndrome and describe the symptom profile of a 35-year-old affected male with an intellectual disability, autism spectrum disorder, and schizophrenia (in association with manic features). This is the first report of psychotic symptoms fully remitting in response to zuclopenthixol therapy in an individual with Kleefstra syndrome. This case is also unique as it demonstrates that functional regression does not necessarily coincide with the development of schizophrenia-like presentations in affected individuals.