Psychotropic Polypharmacy in a 5-Year-Old Boy with a SHANK3 Variant and Complex Mental Health Problems

Background: Dysfunction of the SHANK3 gene has been linked to several neuropsychiatric and neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and epilepsy. SHANK3 haploinsufficiency is the known etiology of Phelan–McDermid syndrome. Case presentation: This report presents a five-year-old boy in whom the c.2062G>C; p.Val688Leu variant was identified in a mosaic state in the SHANK3 gene (40% of heterozygous cells) and classified as a variant of uncertain significance (VUS). The patient was diagnosed with complex mental health problems, which, analogous to typical SHANK3 disruption, included ADHD, oppositional defiant disorder, developmental coordination disorder, Non-REM sleep arousal disorder, insomnia disorder, and avoidant/restrictive food intake disorder. Starting at the age of three years, his psychiatric treatment had included various medication trials over the course of two years. Ultimately, a substantial reduction in emotional outbursts, externalizing behaviors, and parental stress occurred following a multimodal treatment approach comprising psychotropic polypharmacy (PP), i.e., lisdexamfetamine, melatonin, and risperidone, along with behavioral therapy interventions, speech therapy, and occupational therapy. Under this PP, constipation was documented as the only adverse reaction. At the 15-month follow-up, improvements had been quite stable, despite risperidone medication being stopped about 19 weeks after initiation. Conclusions: As shown in this case report, even very young children with complex neuropsychiatric problems and SHANK3 variants might not be treated sufficiently by therapeutic interventions alone, but might require a combination of therapeutic and psychopharmacological interventions to achieve a substantial symptom reduction. However, PP must be approached with a high degree of caution and subjected to close monitoring in children with SHANK3 variants, who are susceptible to an elevated risk of adverse outcomes. Moreover, given the paucity of research in this population, it seems advisable to follow prevailing general guidelines in child and adolescent psychiatry.