Expansion of the phenotypic spectrum of KARS1-related disorders to include arthrogryposis multiplex congenita and summary of experiences with lysine supplementation.

There are currently multiple disorders of aminoacyl-tRNA synthetases described, including KARS1-related disorder resulting from dysfunctional lysyl-tRNA synthetases. In this report, we describe four novel KARS1 variants in three affected individuals, two of whom displayed arthrogryposis-like phenotypes, suggestive of phenotypic expansion. We also highlight subjective clinical improvement in one subject following lysine supplementation in conjunction with a protein-fortified diet, suggesting its potential as a novel treatment modality for KARS1-related disorders. This report offers additional insight into the etiology and management of KARS1-related disorders and expands our ability to provide guidance to affected individuals and their families.

Breaking Barriers to Rapid Whole Genome Sequencing in Pediatrics: Michigan's Project Baby Deer.

The integration of precision medicine in the care of hospitalized children is ever evolving. However, access to new genomic diagnostics such as rapid whole genome sequencing (rWGS) is hindered by barriers in implementation. Michigan's Project Baby Deer (PBD) is a multi-center collaborative effort that sought to break down barriers to access by offering rWGS to critically ill neonatal and pediatric inpatients in Michigan. The clinical champion team used a standardized approach with inclusion and exclusion criteria, shared learning, and quality improvement evaluation of the project's impact on the clinical outcomes and economics of inpatient rWGS. Hospitals, including those without on-site geneticists or genetic counselors, noted positive clinical impacts, accelerating time to definitive treatment for project patients. Between 95-214 hospital days were avoided, net savings of $4155 per patient, and family experience of care was improved. The project spurred policy advancement when Michigan became the first state in the United States to have a Medicaid policy with carve-out payment to hospitals for rWGS testing. This state project demonstrates how front-line clinician champions can directly improve access to new technology for pediatric patients and serves as a roadmap for expanding clinical implementation of evidence-based precision medicine technologies.

Healthcare Professionals' Attitudes toward Rapid Whole Genome Sequencing in Pediatric Acute Care.

We aimed to characterize knowledge and attitudes about rapid whole genome sequencing (rWGS) implementation of a broad constituency of healthcare professionals at hospitals participating in a statewide initiative to implement rWGS for hospitalized neonates and children up to 18 years of age meeting clinical criteria for testing. We surveyed 307 healthcare professionals from eight hospitals about their knowledge and attitudes regarding rWGS. We examined survey internal reliability using exploratory factor analysis and associations between respondent characteristics and attitudes toward rWGS with linear regression. We thematically analyzed free-text responses. Views about rWGS implementation in respondents' own setting and respondents' personal capability to implement rWGS were generally neutral (M = 3.44 (SD = 0.74); M = 3.30 (SD = 0.85), respectively). Views about the potential for rWGS in clinical practice were overall positive (M = 4.12 (SD = 0.57)). The degree of positivity of attitudes about rWGS was strongly influenced by perceived knowledge, clinical or non-clinical role, concerns about future insurance coverage for rWGS as a first-tier test, and future adverse impact of genomics health information on patients or families. We identified several actionable factors influencing attitudes toward rWGS of pediatric healthcare professionals. Expanded education and ongoing implementation research are needed for the full potential of rWGS in pediatrics to be realized.