Genomics-informed Neuropsychiatric Care for Neurodevelopmental Disorders: Results from A Multidisciplinary Clinic

Abstract

Background: Patients with neurodevelopmental disorders (NDDs) have high rates of neuropsychiatric comorbidities that can be highly impairing and treatment refractory. Genomic medicine may help guide care, as pathogenic variants are identified in up to 50% of patients with NDDs. We evaluate the impact of a genomics-informed, multidisciplinary, neuropsychiatric specialty clinic on the diagnosis and management of patients with NDDs. Methods: We performed a retrospective study of 316 patients from the UCLA Care and Research in Neurogenetics Clinic, a genomics-informed multidisciplinary clinic composed of psychiatry, neurology, medical genetics, psychology, and social work. Results: We observed high rates of psychiatric and medical comorbidity. Among the 246 patients that underwent genetic testing, 41.8% had a pathogenic or likely pathogenic (P/LP) variant. Patients had 62 different genetic diagnoses, with 12 diagnoses shared by two or more patients, including Duplication 15q syndrome (9.18%), Tuberous Sclerosis Complex (3.48%), and Angelman syndrome (1.27%), while 50 diagnoses were found in only single patients. Genetic diagnosis resulted in direct changes to clinical management in all patients with a P/LP variant, including high rates of cascade testing (30.6%), family counseling (22.2%), medication changes (13.9%), clinical trial referral (2.8%), medical surveillance (30.6%), and specialty referrals (69.4%). Conclusions: A genomics-informed model can provide significant clinical benefits to patients with NDDs, directly impacting management across multiple domains for most diagnosed patients. As precision treatments for NDDs advance, establishing a genetic diagnosis will be critical for proper management. With the growing number of rare neurogenetic disorders, clinician training should emphasize core principles of genomic medicine over individual syndromes.