Risperidone-Induced Paradoxical Agitation in a Child With Lamb–Shaffer Syndrome, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder: A Case Report

Lamb-Shaffer syndrome (LAMSHF) is a rare autosomal dominant neurodevelopmental disorder caused by haploinsufficiency of the SOX5 gene on chromosome 12p12.1 and characterized by global developmental delay, intellectual disability, speech and language impairment, and frequent behavioral disturbances, including autistic traits and attention deficits. Data on psychotropic response profiles in Lamb-Shaffer syndrome are extremely limited. We report a six-year-five-month-old boy with de novo Lamb-Shaffer syndrome, autism spectrum disorder (ASD) of mild-to-moderate severity, attention deficit hyperactivity disorder, and query intellectual disability who developed paradoxical behavioral activation after initiation of very low-dose risperidone oral solution (0.12 mg once daily) for mild-to-moderate irritability, aggression, and self-injurious head banging. Shortly after treatment initiation, he exhibited marked agitation, increased hyperactivity, worsening aggression and self-injury, insomnia, restlessness, amplification of stereotypic movements, emotional lability, and prolonged crying episodes, clearly exceeding his baseline behavioral pattern and temporally associated with dosing. Clinical assessment and available laboratory investigations, including complete blood counts, liver and renal function tests, electrolytes, thyroid function, bone profile, vitamin B12, vitamin D, lactate, and ammonia, did not reveal metabolic, endocrine, or infectious etiologies. Risperidone was discontinued with subsequent resolution of the paradoxical symptoms and return to baseline. He was then switched to aripiprazole (2 mg once daily for 10 days, then 5 mg once daily), with gradual moderate-to-marked improvement in irritability and self-injurious behavior and no recurrence of agitation over several months of follow-up. To our knowledge, this is the first reported case of risperidone-induced paradoxical activation in a child with Lamb-Shaffer syndrome. This case highlights the need for cautious antipsychotic use and close monitoring in rare genetic neurodevelopmental disorders and suggests that aripiprazole may represent a viable alternative when risperidone is poorly tolerated.