Genomics-informed neuropsychiatric care for neurodevelopmental disorders: Results from a multidisciplinary clinic

Aaron D Besterman; David J Adams; Nicole R Wong; Benjamin N Schneider; Sunil Mehta; Charlotte DiStefano; Rujuta B Wilson; Julian A Martinez-Agosto; Shafali S Jeste

doi:10.1016/j.gim.2024.101333

Genomics-informed neuropsychiatric care for neurodevelopmental disorders: Results from a multidisciplinary clinic

Genet Med. 2024 Dec 16:101333. doi: 10.1016/j.gim.2024.101333. Online ahead of print.

Authors

Aaron D Besterman¹, David J Adams², Nicole R Wong³, Benjamin N Schneider², Sunil Mehta⁴, Charlotte DiStefano⁵, Rujuta B Wilson², Julian A Martinez-Agosto⁶, Shafali S Jeste⁷

Affiliations

¹ Division of Child and Adolescent Psychiatry, University of California San Diego Department of Psychiatry, San Diego, CA; Rady Children's Hospital of San Diego, San Diego, CA; Rady Children's Institute for Genomic Medicine, San Diego, CA.
² David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA.
³ Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD.
⁴ PrairieCare Meidcal Group, Rochester, MN.
⁵ Department of Psychiatry, Children's Hospital Los Angeles, Los Angeles, CA; Department of Psychiatry & The Biobehavioral Sciences, University of Southern California, Los Angeles, CA.
⁶ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA; Department of Human Genetics, University of California Los Angeles, Los Angeles, CA. Electronic address: julianmartinez@mednet.ucla.edu.
⁷ Division of Neurology, Children's Hospital Los Angeles, Los Angeles, CA; Departments of Pediatrics and Neurology, University of Southern California, Los Angeles, CA. Electronic address: sjeste@chla.usc.edu.

PMID: 39692675
DOI: 10.1016/j.gim.2024.101333

Abstract

Purpose: Patients with neurodevelopmental disorders (NDDs) have high rates of neuropsychiatric comorbidities. Genomic medicine may help guide care because 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 University of California, Los Angeles Care and Research in Neurogenetics Clinic, a genomics-informed multidisciplinary clinic.

Results: Among the 246 patients who underwent genetic testing, 41.8% had a pathogenic or likely pathogenic variant. Patients had 62 different genetic diagnoses, with 12 diagnoses shared by 2 or more patients, whereas 50 diagnoses were found in only single patients. Genetic diagnosis resulted in direct changes to clinical management in all patients with a pathogenic or likely pathogenic variant, including 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 affecting management across multiple domains for most diagnosed patients. As precision treatments 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.

Keywords: Genetic testing; Multidisciplinary care; Neurodevelopmental disorders; Neuropsychiatry; Precision medicine.