Newborn Sequencing in Genomic Medicine and Public Health

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening

Stanford-Binet and WAIS IQ differences and their implications for adults with intellectual disability (aka mental retardation)

Els components de diferents equips de la Congregació fent un vermut de germanor, veiem entre altres a Joan González, Ricard Farré, Antoni Bofill, Francesc Almiñana, Joan Pérez, Lluís Tortajada i Dídac Ramos

Outcome measures for clinical trials in fragile X syndrome.

OBJECTIVE: Progress in basic neuroscience has led to identification of molecular targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental disorders; however, there is a gap in translation to targeted therapies in humans. One major obstacle to the demonstration of efficacy in human trials has been the lack of generally accepted endpoints to assess improvement in function in individuals with FXS. To address this problem, the National Institutes of Health convened a meeting of leading scientists and clinicians with the goal of identifying and standardizing outcome measures for use as potential endpoints in clinical trials in FXS. METHODS: Participants in the meeting included FXS experts, experts in the design and implementation of clinical trials and measure development, and representatives from advocacy groups, industry, and federal agencies. RESULTS: The group generated recommendations for optimal outcome measures in cognitive, behavioral, and biomarker/medical domains, including additional testing and validation of existing measures and development of new measures in areas of need. Although no one endpoint or set of endpoints could be identified that met all criteria as an optimal measure, recommendations are presented in this report. CONCLUSION: The report is expected to guide the selection of measures in clinical trials and lead to the use of a more consistent battery of measures across trials. Furthermore, this will help to direct research toward gaps in the development of validated FXS-specific outcome measures and to assist with interpretation of clinical trial data by creating templates for measurement of treatment efficacy

Outcome measures for clinical trials in fragile X syndrome.

ObjectiveProgress in basic neuroscience has led to identification of molecular targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental disorders; however, there is a gap in translation to targeted therapies in humans. One major obstacle to the demonstration of efficacy in human trials has been the lack of generally accepted endpoints to assess improvement in function in individuals with FXS. To address this problem, the National Institutes of Health convened a meeting of leading scientists and clinicians with the goal of identifying and standardizing outcome measures for use as potential endpoints in clinical trials in FXS.MethodsParticipants in the meeting included FXS experts, experts in the design and implementation of clinical trials and measure development, and representatives from advocacy groups, industry, and federal agencies.ResultsThe group generated recommendations for optimal outcome measures in cognitive, behavioral, and biomarker/medical domains, including additional testing and validation of existing measures and development of new measures in areas of need. Although no one endpoint or set of endpoints could be identified that met all criteria as an optimal measure, recommendations are presented in this report.ConclusionThe report is expected to guide the selection of measures in clinical trials and lead to the use of a more consistent battery of measures across trials. Furthermore, this will help to direct research toward gaps in the development of validated FXS-specific outcome measures and to assist with interpretation of clinical trial data by creating templates for measurement of treatment efficacy

Outcome Measures for Clinical Trials in Down Syndrome

Increasingly individuals with intellectual and developmental disabilities, including Down syndrome, are being targeted for clinical trials. However, a challenge exists in effectively evaluating the outcomes of these new pharmacological interventions. Few empirically evaluated, psychometrically sound outcome measures appropriate for use in clinical trials with individuals with Down syndrome have been identified. To address this challenge, the National Institutes of Health (NIH) assembled leading clinicians and scientists to review existing measures and identify those that currently are appropriate for trials; those that may be appropriate after expansion of age range addition of easier items, and/or downward extension of psychometric norms; and areas where new measures need to be developed. This article focuses on measures in the areas of cognition and behavior

Acute management of propionic acidemia.

Propionic Acidemia or aciduria is an intoxication-type disorder of organic metabolism. Patients deteriorate in times of increased metabolic demand and subsequent catabolism. Metabolic decompensation can manifest with lethargy, vomiting, coma and death if not appropriately treated. On January 28-30, 2011 in Washington, D.C., Children's National Medical Center hosted a group of clinicians, scientists and parental group representatives to design recommendations for acute management of individuals with Propionic Acidemia. Although many of the recommendations are geared towards the previously undiagnosed neonate, the recommendations for a severely metabolically decompensated individual are applicable to any known patient as well. Initial management is critical for prevention of morbidity and mortality. The following manuscript provides recommendations for initial treatment and evaluation, a discussion of issues concerning transport to a metabolic center (if patient presents to a non-metabolic center), acceleration of management and preparation for discharge

Newborn Sequencing in Genomic Medicine and Public Health.

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening