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Capturing the clinical utility of genomic testing: medical recommendations following pediatric microarray.

ABSTRACT: Interpretation of pediatric chromosome microarray (CMA) results presents diagnostic and medical management challenges. Understanding management practices triggered by CMA will inform clinical utility and resource planning. Using a retrospective cohort design, we extracted clinical and management-related data from the records of 752 children with congenital anomalies and/or developmental delay who underwent CMA in an academic pediatric genetics clinic (2009-2011). Frequency distributions and relative rates (RR) of post-CMA medical recommendations in children with reportable and benign CMA results were calculated. Medical recommendations were provided for 79.6% of children with reportable results and 62.0% of children with benign results. Overall, recommendations included specialist consultation (40.8%), imaging (32.5%), laboratory investigations (17.2%), surveillance (4.6%), and family investigations (4.9%). Clinically significant variants and variants of uncertain clinical significance were associated with higher and slightly higher rates of management recommendations, respectively, compared with benign/no variants (RR=1.34; 95% CI (1.22-1.47); RR=1.23; 95% CI (1.09-1.38)). Recommendation rates for clinically significant versus uncertain results depended upon how uncertainty was classified (RRbroad=1.09; 95% CI (0.99-1.2); RRnarrow=1.12; 95% CI (1.02-1.24)). Recommendation rates also varied by the child's age and provider type. In conclusion, medical recommendations follow CMA for the majority of children. Compared with benign CMA results, clinically significant CMA variants are a significant driver of pediatric medical recommendations. Variants of uncertain clinical significance drive recommendations, but to a lesser extent. As a broadening range of specialists will need to respond to CMA results, targeted capacity building is warranted.

SUBMITTER: Hayeems RZ

PROVIDER: S-EPMC4538218 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Project description:ImportanceClinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known.ObjectiveTo investigate the value of reinterpreting previously reported genomic test results.Design, setting, and participantsThis study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017.Main outcomes and measuresPatient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant.ResultsA total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8%] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2%) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3%) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1%) with a genetic diagnosis and 48 of 124 patients (38.7%) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0%) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8%) with a VUS.Conclusions and relevanceThe identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years.

Project description:BackgroundChildren and adolescents with upper limb impairments can experience limited bimanual performance reducing daily-life independence. We have developed a fully wearable pediatric hand exoskeleton (PEXO) to train or compensate for impaired hand function. In this study, we investigated its appropriateness, practicability, and acceptability.MethodsChildren and adolescents aged 6-18 years with functional limitations in at least one hand due to a neurological cause were selected for this cross-sectional evaluation. We characterized participants by various clinical tests and quantified bimanual performance with the Assisting Hand Assessment (AHA). We identified children whose AHA scaled score increased by ≥ 7 points when using the hand exoskeleton and determined clinical predictors to investigate appropriateness. The time needed to don each component and the number of technical issues were recorded to evaluate practicability. For acceptability, the experiences of the patients and the therapist with PEXO were evaluated. We further noted any adverse events.ResultsEleven children (median age 11.4 years) agreed to participate, but data was available for nine participants. The median AHA scaled score was higher with PEXO (68; IQR: 59.5-83) than without (55; IQR: 37.5-80.5; p = 0.035). The Box and Block test, the Selective Control of the Upper Extremity Scale, and finger extensor muscle strength could differentiate well between those participants who improved in AHA scaled scores by ≥ 7 points and those who did not (sensitivity and specificity varied between 0.75 and 1.00). The median times needed to don the back module, the glove, and the hand module were 62, 150, and 160 s, respectively, but all participants needed assistance. The most critical failures were the robustness of the transmission system, the electronics, and the attachment system. Acceptance was generally high, particularly in participants who improved bimanual performance with PEXO. Five participants experienced some pressure points. No adverse events occurred.ConclusionsPEXO is a safe exoskeleton that can improve bimanual hand performance in young patients with minimal hand function. PEXO receives high acceptance. We formulated recommendations to improve technical issues and the donning before such exoskeletons can be used under daily-life conditions for therapy or as an assistive device. Trial registration Not appropriate.

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Capturing the clinical utility of genomic testing: medical recommendations following pediatric microarray.

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