Learning to make a difference for chILD: Value creation through network collaboration and team science.

Addressing the recognized challenges and inequalities in providing high quality healthcare for rare diseases such as children's interstitial lung disease (chILD) requires collaboration across institutional, geographical, discipline, and system boundaries. The Children's Interstitial Lung Disease Respiratory Network of Australia and New Zealand (chILDRANZ) is an example of a clinical network that brings together multidisciplinary health professionals for collaboration, peer learning, and advocacy with the goal of improving the diagnosis and management of this group of rare and ultra-rare conditions. This narrative review explores the multifaceted benefits arising from social learning spaces within rare disease clinical networks by applying the value creation framework. The operation of the chILDRANZ network is used as an example across the framework to highlight how value is generated, realized, and transferred within such collaborative clinical and research networks. The community of practice formed in the chILDRANZ multidisciplinary meetings provides a strong example of social learning that engages with the uncertainty inherent in rare disease diagnosis and management and pays attention to generate new knowledge and best practice to make a difference for children and families living with chILD. This review underscores international calls for further investment in, and support of, collaborative clinical networks and virtual centers of excellence for rare disease.

The role of exome sequencing in childhood interstitial or diffuse lung disease.

BACKGROUND: Children's interstitial and diffuse lung disease (chILD) is a complex heterogeneous group of lung disorders. Gene panel approaches have a reported diagnostic yield of ~ 12%. No data currently exist using trio exome sequencing as the standard diagnostic modality. We assessed the diagnostic utility of using trio exome sequencing in chILD. We prospectively enrolled children meeting specified clinical criteria between 2016 and 2020 from 16 Australian hospitals. Exome sequencing was performed with analysis of an initial gene panel followed by trio exome analysis. A subset of critically ill infants underwent ultra-rapid trio exome sequencing as first-line test. RESULTS: 36 patients [median (range) age 0.34 years (0.02-11.46); 11F] were recruited from multiple States and Territories. Five patients had clinically significant likely pathogenic/pathogenic variants (RARB, RPL15, CTCF, RFXANK, TBX4) and one patient had a variant of uncertain significance (VIP) suspected to contribute to their clinical phenotype, with VIP being a novel gene candidate. CONCLUSIONS: Trio exomes (6/36; 16.7%) had a better diagnostic rate than gene panel (1/36; 2.8%), due to the ability to consider a broader range of underlying conditions. However, the aetiology of chILD in most cases remained undetermined, likely reflecting the interplay between low penetrant genetic and environmental factors.

Genomic testing for children with interstitial and diffuse lung disease (chILD): parent satisfaction, understanding and health-related quality of life.

OBJECTIVE: Research is needed to determine best practice for genomic testing in the context of child interstitial or diffuse lung disease (chILD). We explored parent's and child's health-related quality of life (HRQoL), parents' perceived understanding of a genomic testing study, satisfaction with information and the study and decisional regret to undertake genomic testing. METHODS: Parents of children with diagnosed or suspected chILD who were enrolled in a genomic sequencing study were invited to complete questionnaires pretesting (T1) and after receiving the result (T2). RESULTS: Parents' (T1, n=19; T2, n=17) HRQoL was lower than population norms. Study satisfaction (T1) and perceived understanding (T2) were positively correlated (rs=0.68, p=0.014). Satisfaction with information (T1 and T2) and decisional regret (T2) were negatively correlated (T1 rs=-0.71, p=0.01; T2 rs=-0.56, p=0.03). Parents reported wanting more frequent communication with staff throughout the genomic sequencing study, and greater information about the confidentiality of test results. CONCLUSIONS: Understanding of genomic testing, satisfaction with information and participation and decisional regret are inter-related. Pretest consultations are important and can allow researchers to explain confidentiality of data and the variable turnaround times for receiving a test result. Staff can also update parents when there will be delays to receiving a result.

A systematic review of geographical inequities for accessing clinical genomic and genetic services for non-cancer related rare disease.

Place plays a significant role in our health. As genetic/genomic services evolve and are increasingly seen as mainstream, especially within the field of rare disease, it is important to ensure that where one lives does not impede access to genetic/genomic services. Our aim was to identify barriers and enablers of geographical equity in accessing clinical genomic or genetic services. We undertook a systematic review searching for articles relating to geographical access to genetic/genomic services for rare disease. Searching the databases Medline, EMBASE and PubMed returned 1803 papers. Screening led to the inclusion of 20 articles for data extraction. Using inductive thematic analysis, we identified four themes (i) Current service model design, (ii) Logistical issues facing clinicians and communities, (iii) Workforce capacity and capability and iv) Rural culture and consumer beliefs. Several themes were common to both rural and urban communities. However, many themes were exacerbated for rural populations due to a lack of clinician access to/relationships with genetic specialist staff, the need to provide more generalist services and a lack of genetic/genomic knowledge and skill. Additional barriers included long standing systemic service designs that are not fit for purpose due to historically ad hoc approaches to delivery of care. There were calls for needs assessments to clarify community needs. Enablers of geographically equitable care included the uptake of new innovative models of care and a call to raise both community and clinician knowledge and awareness to demystify the clinical offer from genetics/genomics services.