Background <p>This case report addresses a clinical gap in the management of severe challenging behaviors (CBs) in Xia–Gibbs Syndrome (XGS), a rare genetic disorder caused by variants in the AHDC1 gene, highlighting the importance of integrative, multidisciplinary assessment to disentangle overlapping medical, developmental, and psychiatric contributors.</p> Case presentation <p>A 17-year-old French adolescent girl of Chinese descent with XGS and intellectual development disorder was referred to inpatient care for severe CBs and suspected schizophrenia. A comprehensive assessment of pain-related factors led to the identification and treatment of several co-occurring medical conditions (gastritis, local care for atopic dermatitis, progestin for dysmenorrhea). Prolonged clinical observations showed that most psychotic-like symptoms resulted instead from developmentally appropriate stress-coping strategies and depressive symptoms. Other identified risk factors for CBs were medication side effects, unmet sensory integration needs, and environmental stressors. Providing interventions on all these factors associated with environmental adaptations and optimized developmental care led to marked clinical improvement.</p> Conclusions <p>This case illustrates that in patients with complex neurodevelopmental disorders, comprehensive medical assessment should be prioritized over psychiatric assessment when possible, considering symptoms overlap and communication difficulties. As most risk factors for CBs can mutually reinforce and self-sustain, integrative care for these patients should consider concomitant interventions targeting both risk factors and CBs themselves.</p>