The yield of genetic workup for middle-aged and elderly patients with neurological disorders in a real-world setting

• DOI: 10.1016/j.jns.2024.123074
• Publication Date: 2024-05-31T15:51:14Z
• Authors: Noga Lempel; Shahar Shelly; Odelia Chorin; Rachel Rock; Aviva Eliyahu; Yael Finezilber; Hana Poran; Neta Feinstein-Goren; Meirav Segev; Haike Reznik-Wolf; Ortal Barel; David Orion; Saar Anis; Miriam Regev; Hagith Yonath; Dan Dominissini; Ilan Blatt; Sharon Hassin-Baer; Amir Dori; Elon Pras; Lior Greenbaum

Genetic workup is becoming increasingly common in the clinical assessment of neurological disorders. We evaluated its yield among middle-aged and elderly neurological patients, in a real-world context. This retrospective study included 368 consecutive Israeli patients aged 50 years and older (202 [54.9%] males), who were referred to a single neurogenetics clinic between 2017 and mid-2023. All had neurological disorders, without a previous molecular diagnosis. Demographic, clinical and genetic data were collected from medical records. The mean age at first genetic counseling at the clinic was 62.3 ± 7.8 years (range 50-85 years), and the main indications for referral were neuromuscular, movement and cerebrovascular disorders, as well as cognitive impairment and dementia. Out of the 368 patients, 245 (66.6%) underwent genetic testing that included exome sequencing (ES), analysis of nucleotide repeat expansions, detection of specific mutations, targeted gene panel sequencing or chromosomal microarray analysis. Overall, 80 patients (21.7%) received a molecular diagnosis due to 36 conditions, accounting for 32.7% of the patients who performed genetic testing. The diagnostic rates were highest for neuromuscular (58/186 patients [31.2%] in this group, 39.2% of 148 tested individuals) and movement disorders (14/79 [17.7%] patients, 29.2% of 48 tested), but lower for other disorders. Testing of nucleotide repeat expansions and ES provided a diagnosis to 28/73 (38.4%) and 19/132 (14.4%) individuals, respectively. Based on our findings, genetic workup and testing are useful in the diagnostic process of neurological patients aged ≥50 years, in particular for those with neuromuscular and movement disorders.