Background FOXP1 syndrome is a genetic neurodevelopmental disorder associated with complex clinical presentations including global developmental delay, mild to profound intellectual disability, speech and language impairment, autism traits, attention-deficit/hyperactivity disorder (ADHD), and a range of behavioral challenges.. To date, much of the literature focuses on childhood symptoms and little is known about the FOXP1 syndrome phenotype in adolescence or adulthood. Methods A series of caregiver interviews and standardized questionnaires assessed psychiatric and behavioral features of 20 adolescents and adults with FOXP1 syndrome. Interviews captured change in various psychiatric manifestations over time. Medication, social, educational, and vocational history was collected and visual analog scales measured top caregiver concerns during childhood and adolescence/adulthood. Results Anxiety and externalizing behaviors were common in this cohort and psychiatric features, such as psychosis or bipolar symptoms, were present in two participants. There was no reported regression or loss of skills, early in development or during adolescence/adulthood. Caregivers reported continued development in adaptive skills even into adolescence/adulthood. Medication use was common particularly for features of ADHD, although multiple trials were required for some participants to achieve benefit. Standardized assessments accurately picked up on externalizing symptoms and were less sensitive to internalizing symptoms. Educational setting varied up until late elementary school and gradually shifted to special education. Cognitive and developmental concerns were reported as primary during childhood and independence/safety and housing concerns became top concerns by adolescence/adulthood. Caregivers reported continued development in adaptive skills even into adulthood. Conclusions Taken together, results are reassuring, with many families reporting their adolescent and adult children continued to gain skills over time, particularly related to increased independence in communication and personal care. There were no reports of developmental regression, neuropsychiatric decompensation or catatonia.

TL receives funding from the Phelan-McDermid Syndrome Foundation and is on the advisory board of the CHAMP1 research foundation. AK is on the Advisory Board for the Klingenstein Third Generation Foundation, Ovid Therapeutics, David Lynch Foundation, ADNP Kids Research Foundation, and Ritrova Therapeutics and consults to Acadia, Alkermes, Jaguar Therapeutics, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, Scioto Biosciences, and Biogen. PMS is a developer of the Sensory Assessment for Neurodevelopmental Disorders, which is licensed by Mount Sinai to Stoelting, Co. JDB consults to BridgeBio, holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary professorship from Aarhus University Denmark, receives research support from Takeda and Oryzon, and is a journal editor for Springer Nature.

This study was funded by the Beatrice and Samuel A Seaver Foundation.

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