'Exome first' approach can reduce diagnostic costs and time - retrospective single centre analysis of 111 individuals with rare neurodevelopmental disorders

Abstract

This single center study aims to determine the time, diagnostic procedure and cost saving potential of early exome sequencing in a cohort of 111 individuals with genetically confirmed neurodevelopmental disorders. We retrospectively collected data regarding diagnostic time points and procedures from the individuals medical histories and developed criteria for classifying diagnostic procedures in terms of requirement, followed by a cost allocation. The genetic variants of all individuals were reevaluated according to ACMG recommendations and considering the individuals phenotype. Individuals who developed first symptoms of their underlying genetic disorder when Next Generation Sequencing (NGS) diagnostics were already available received a diagnosis significantly faster than individuals with first symptoms before this cutoff. The largest amount of potentially dispensable diagnostics was found in genetic, metabolic, and cranial magnetic resonance imaging examinations. Out of 407 performed genetic examinations, 296 (72.7%) were classified as potentially dispensable. The same applied to 36 (27.9%) of 129 cranial magnetic resonance imaging and 111 (31.8%) of 349 metabolic examinations. Dispensable genetic examinations accounted 302,947.07{euro} (90.2%) of the total 335,837.49{euro} in potentially savable costs in this cohort. The remaining 32,890.42{euro} (9.8%) are related to non-required metabolic and cranial magnetic resonance imaging diagnostics. On average, the total potentially savable costs in our study amount to {euro}3,025.56 per individual. Cost savings by first tier exome sequencing lie primarily in genetic, metabolic, and cMRI testing in this German cohort, underscoring the utility of performing exome sequencing at the beginning of the diagnostic pathway and the potential for saving diagnostic costs and time.