Unmasked Behavioral Disturbance Following Traumatic Brain Injury in an Adult With Previously Undiagnosed Sotos Syndrome.

Sotos syndrome is a rare autosomal dominant disorder characterized by childhood overgrowth, including tall stature and macrocephaly, distinctive facial appearance, and neuropsychiatric manifestations. These features include intellectual disability and a broad spectrum of behavioral disturbances. Traumatic brain injury (TBI) is also known to cause various neuropsychiatric symptoms, including behavioral disturbances, even in individuals without underlying medical conditions. However, the influence of pre-existing neurodevelopmental disorders such as Sotos syndrome on behavioral outcomes following TBI remains incompletely understood. We report the case of a 35-year-old man with previously undiagnosed Sotos syndrome who developed severe behavioral disturbances following TBI. Based on his history of childhood overgrowth and characteristic dysmorphic facial features, Sotos syndrome was suspected and subsequently confirmed by genetic testing, which demonstrated a heterozygous whole-gene deletion of the causative gene, NSD1. Initial treatment with yokukansan and olanzapine did not improve his symptoms. However, subsequent treatment with valproate and propranolol resulted in marked improvement. The total Neuropsychiatric Inventory Questionnaire (NPI-Q) score decreased from 43 to 15 after one year of treatment. This report suggests that TBI may unmask or exacerbate behavioral disturbances in individuals with underlying neurodevelopmental disorders such as Sotos syndrome. In addition, a combination of valproate and propranolol may represent a potential therapeutic option for managing severe behavioral symptoms following TBI, although further accumulation of cases is required to establish its efficacy.