Exome first approach to reduce diagnostic costs and time – retrospective analysis of 111 individuals with rare neurodevelopmental disorders

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. All genetic variants were re-evaluated 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€ (90.2%) of the total 335,837.49€ in potentially savable costs in this cohort. The remaining 32,890.42€ (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 €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.

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

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.

Peripheral and Central Smell Regions in Migraine Patients using Maraş Powder (Smokeless Tobacco): A Magnetic Resonance Imaging Evaluation

Objective In the present study, we investigated the efficacy of Maraş powder (smokeless tobacco) use on smell regions in migraine patients. Methods The cranial magnetic resonance imaging images of 58 adult patients were included in this retrospective study. Thirty-eight of them were migraine patients (18 of them using Maraş powder and 20 of them not using Maraş powder) and 20 of them were healthy controls. Bilateral peripheral (olfactory bulb [OB] volume and olfactory sulcus depth) and central smell regions (insular gyrus area and corpus amygdala area) as well as nasal septal deviation were evaluated. Results In migraine patients (using or not using Maraş powder), OB volumes, and in Maraş powder using migraine patients, corpus amygdala areas were lower than those in the control group (p < 0.05). In Maraş powder-using migraine patients, left insular gyrus areas of the females were significantly lower than the males (p < 0.05). Conclusion We concluded that the peripheral smell region of the OB volume decreased in migraine patients (using or not using Maraş powder). However, the central smell region of corpus amygdala area decreased in Maraş powder using migraine patients. Maraş powder usage may increase vascular shrinkage, and the decrease in OB volume and corpus amygdala area becomes prominent. It can be said that Maraş powder usage may cause a size decrease in the peripheral and central smell regions in migraine patients. Therefore, migraine patients and non-migrainous people should be noticed for the harmful effects of Maraş powder on the vascular system and smell system in the aspects of OB volume and corpus amygdala area decrease.