The current standard of care for diagnosis of severe intellectual disability (ID) and epileptic encephalopathy (EE) results in a diagnostic yield of ∼50%. Affected individuals nonetheless undergo multiple clinical evaluations and low-yield laboratory tests often referred to as a 'diagnostic odyssey'. This study was aimed at assessing the utility of clinical whole-exome sequencing (WES) in individuals with undiagnosed and severe forms of ID and EE, and the feasibility of its implementation in routine practice by a small regional genetic center. We performed WES in a cohort of 43 unrelated individuals with undiagnosed ID and/or EE. All individuals had undergone multiple clinical evaluations and diagnostic tests over the years, with no definitive diagnosis. Sequencing data analysis and interpretation were carried out at the local molecular genetics laboratory. The diagnostic rate of WES reached 32.5% (14 out of 43 individuals). Genetic diagnosis had a direct impact on clinical management in four families, including a prenatal diagnostic test in one family. Our data emphasize the clinical utility and feasibility of WES in individuals with undiagnosed forms of ID and EE and highlight the necessity of close collaborations between ordering physicians, molecular geneticists, bioinformaticians and researchers for accurate data interpretation.

Playing-related musculoskeletal disorders (PRMD) in professional musicians are common. Existing literature demonstrates that up to 86 % of musicians are affected. The aim of the study was to evaluate the frequency of musculoskeletal pain in professional orchestral musicians with regard to their instrument affiliation. Of special interest were pain intensity and its association with predictors such as gender, instrument group, age or stage fright. Professional orchestra players completed a self-report questionnaire to assess playing-related musculoskeletal pain and its frequency and intensity in various body regions on a numeric rating scale (NRS). Relative frequencies and prevalence ratios for different instrument groups were estimated. Out of 720 approached musicians, 408 were included in the sample (response rate 57 %); overall, 89.5 % had been affected by current or past playing-related musculoskeletal pain, 62.7 % reported pain in the previous 3 months, and 8.6 % reported current pain. Pain distribution and frequency varied between instrument groups. For all instrument groups, the neck was the most common pain region. About 43 % of musicians presented more than five pain regions, in particular violin players. Approximately 40 % of musicians indicated frequent or permanent pain. Average pain intensities increased from NRS 3.8 up to a range of 5.9 and 7.4 for frequent and permanent pain, respectively. Female gender and stage fright were proven to be predictors for musculoskeletal pain. Professional orchestral musicians are greatly affected by PRMD, often experiencing frequent or permanent pain, high pain levels and pain in various body regions. As PRMD might contribute considerably to performance disability, sick leave and the possibility of premature termination of a musicians' career, this study highlights the necessity for tailored therapeutic and preventive strategies in performing arts medicine.

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