Sudden Death in a Child With Ocular Lesions.

This case report describes a patient treated for ocular lesions who died suddenly at age 8 years and was diagnosed postmortem with Carney complex.

Comparing the frequency of variants of uncertain significance (VUS) between ancestry groups in a paediatric epilepsy cohort.

BACKGROUND: Studies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy, which is increasingly found to be genetic in paediatric populations, and has precision medicine applications. This study examines the differences in the frequency of uncertain next-generation sequencing (NGS) results among a paediatric epilepsy cohort between ancestral groups historically under-represented in biomedical research (UBR) and represented in biomedical research (RBR). METHODS: A retrospective chart review of patients with epilepsy seen at Columbia University Irving Medical Center (CUIMC). One hundred seventy-eight cases met the following criteria: (1) visited any provider within the Pediatric Neurology Clinic at CUIMC, (2) had an ICD code indicating a diagnosis of epilepsy, (3) underwent NGS testing after March 2015 and (4) had self-reported ancestry that fit into a single dichotomous category of either historically represented or under-represented in biomedical research. RESULTS: UBR cases had significantly higher rates of uncertain results when compared with RBR cases (79.2% UBR, 20.8% RBR; p value=0.002). This finding remained true after controlling for potential confounding factors, including sex, intellectual disability or developmental delay, epilepsy type, age of onset, number of genes tested and year of testing. CONCLUSION: Our results add to the literature that individuals who are of ancestries historically under-represented in genetics research are more likely to receive uncertain genetic results than those of represented majority ancestral groups and establishes this finding in an epilepsy cohort.

Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age.

In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well-studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months. CNVs are classified using the American College of Medical Genetics and Genomics guidelines and CNVs in our cohort are compared to an autism spectrum disorder (ASD) cohort, and to a control cohort. Pathogenic CNVs are identified in 5 of 116 cases (4.3%). Variants of uncertain significance (VUS) favoring pathogenic CNVs are identified in 9 cases (7.8%). Several CNVs are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, and schizophrenia. The structural variant 47,XXY is identified in two cases (2/69 boys, 2.9%) not previously diagnosed with Klinefelter syndrome. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls (p = 0.007) and are not significantly different from the ASD cohort. The finding of pathogenic or VUS favoring pathogenic CNVs, or structural variants, in 12.1% of cases, combined with the observation of higher pathogenicity scores for deletions in SUDP versus controls, suggests that CMA should be included in the genetic evaluation of SUDP.

Nature vs. Nurture in Precision Education: Insights of Parents and the Public.

BACKGROUND: The philosophical debate about the roles of nature versus nurture in human flourishing is not new. But the rise of precision education-a growing field of research that encourages the use of genetic data to inform educational trajectory and interventions to better meet student needs-has renewed historical and ethical concerns. A major worry is that "genetic hype" may skew public perceptions toward a deterministic perception of the child's educational trajectory, regardless of the child's capacities, and underestimation of environmental factors affecting educational outcomes. We tested this hypothesis with parents and adults from the general public in the US. METHODS: A newly developed computerized implicit association test (IAT) to assess automatic associations between genetics or environments and student behaviors that are associated with educational achievement was administered to samples of parents of children below 21 years old (n = 450) and adults from the general public (n = 419). The samples were representative of the adult US population and adjusted to oversample Black/African American participants. An overall D score for participants' IATs (range: [-2, 2]) was calculated on the basis of the speed of participants' responses. RESULTS: The mean IAT score for both samples indicated stronger association between the quality of being a good student and environment rather than genetics (parents: mean=-0.146, t = -6.56, p < 0.001; general public: mean = -0.249, t = -9.45, p < 0.0001). Younger participants from the general public showed a stronger association between genetics and educational success than middle-aged participants (ß = -0.301, p = 0.006). CONCLUSION: The views of parents and the general public on behavioral genetics and education are complex but call for investment in creating educational environments that are supportive of student success. Future research is needed to understand differences across age groups and to explore views of other stakeholders involved in determining children's educational trajectories about the roles of nature versus nurture in precision education.