Pediatric Clinics of North America

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Pharmacogenomics, where genomic information is used to tailor medication management, is a strategy to maximize drug efficacy and minimize toxicity. Although pediatric evidence is less robust than for adults, medications influenced by pharmacogenomics are prescribed to children and adolescents. Evidence-based guidelines and drug label annotations are available from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics Knowledgebase (PharmGKB). Some pediatric health care facilities use pharmacogenomics to provide dosing recommendations to pediatricians...

In some relatively common inborn errors of metabolism there can be the accumulation of toxic compounds including ammonia and organic acids such as lactate and ketoacids, as well as energy deficits at the cellular level. The clinical presentation is often referred to as a metabolic emergency or crisis. Fasting and illness can result in encephalopathy within hours, and without appropriate recognition and intervention, the outcome may be permanent disability or death. This review outlines easy and readily available means of recognizing and diagnosing a metabolic emergency as well as general guidelines for management...

Spinal muscular atrophy (SMA) is a progressive disease of the lower motor neurons associated with recessive loss of the SMN1 gene, and which leads to worsening weakness and disability, and is fatal in its most severe forms. Over the past six years, three treatments have emerged, two drugs that modify exon splicing and one gene therapy, which have transformed the management of this disease. When treated pre-symptomatically, many children show normal early motor development, and the benefits extend from the newborn period to adulthood...

Achondroplasia is the most common form of disproportionate severe short stature. Management of achondroplasia requires a multidisciplinary approach and has been largely symptomatic for medical complications and psychosocial implications. Increased understanding of genetic and molecular mechanisms of achondroplasia has led to the development of novel disease-modifying drugs. The current drugs under investigation target the growth plate to stimulate chondrocyte growth and development. These include analogs of C-type natriuretic peptide (CNP), FGFR3-selective tyrosine kinase inhibitors, anti-FGFR3 antibodies, aptamers against FGF2, and soluble forms of FGFR3...

Neurofibromatosis type I (NF1) is a common dominantly inherited disorder, and one of the most common of the RASopathies. Most individuals with NF1 develop plexiform neurofibromas and cutaneous neurofibromas, nerve tumors caused by NF1 loss of function in Schwann cells. Cell culture models and mouse models of NF1 are being used to test drug efficacy in preclinical trials, which led to Food and Drug Administration approval for use of MEK inhibitors to shrink most inoperable plexiform neurofibromas. This article details methods used for testing in preclinical models, and outlines newer models that may identify additional, curative, strategies...

As the availability of advanced molecular testing like whole exome and genome sequencing expands, it comes with the added complication of interpreting inconclusive results, including determining the relevance of variants of uncertain significance or failing to find a variant in an otherwise suspected specific genetic disorder. This complication necessitates the use of alternative testing methods to gather more information in support of, or against, a particular genetic diagnosis. Therefore, new genome-wide approaches, including DNA epigenetic testing, RNA sequencing, and metabolomics, are increasingly being used to increase the diagnostic yield when used in conjunction with more conventional genetic tests...

Receiving a genetic diagnosis can be challenging for parents as they learn to cope and adapt to this news. They often experience a myriad of emotions ranging from shock to relief. Yet overwhelmingly, parents report a negative experience with this process. Factors that improve parental satisfaction include being provided written information, emotional and psychosocial support, and connections with other parents. Genetics care providers are particularly equipped to solicit parental needs and provide support before, during, and after receiving a diagnosis...

Selecting the ideal test to evaluate an individual with a suspected genetic disorder can be challenging. While several clinical testing options are available, no single test yet captures all potentially causative genetic variants. Thus, clinicians may order testing in a stepwise fashion, and what to order after non-diagnostic testing can be challenging to determine. Here, we provide an overview of commonly used clinical genetic tests, guidance on when they are best used, and what they may miss. We conclude with a discussion of how new technologies might be used to identify challenging variants and simplify clinical testing in the future...

Although genetics has traditionally been associated with pregnancy, birth defects, and newborn screening, almost every disease is influenced in part by an individual's genetic makeup. Therefore, it is important to consider the impact of genetics in health and disease throughout an individual's lifetime.

In the last few decades, medical genetics has undergone a revolution because of the development of technologies and informatics approaches that can generate and analyze large amounts of genomic data. Pediatricians have been hugely affected by these changes. The early age of presentation for birth defects and neurocognitive disorders, together with a shortage of trained genetics professionals, has increased consultations for conditions with a genetic cause, not only in pediatric practice but also in other subspecialties...

Family history and physical exam findings are often the first clues that prompt medical providers to consider clinical genetics evaluation. There is standardized nomenclature for both the pedigree and description of physical features. Systematic evaluation of patients through obtaining family history and careful physical examination is essential to the formulation of a differential diagnosis and plan in the clinical genetics evaluation. The goal of this article is to provide an overview of family history and dysmorphology exam, and their relevance for the clinical genetics evaluation...

Pediatric health care providers caring for patients and families with genetic disease will encounter a range of ethical issues. These include traditional pediatric health care issues, such as surrogate decision making and end-of-life care. Genetic testing raises the importance of informed consent for potential risks that move beyond the oft discussed physical risks and into longer term concepts such as psychological impact, privacy and potential discrimination. Predictive testing in childhood also raises questions of whether the child has an autonomy interest in delaying testing until they have decision making capacity to do so on their own...

The goal of newborn screening is to identify medical conditions that can cause significant morbidity and/or mortality if not treated early in life. Pediatricians often play a vital role in the initial disclosure of newborn screening results and coordination of confirmatory testing, treatment, and referral to specialty care. The goal of this article is to provide an overview of current newborn screening in the United States, focusing on the various disorders, their manifestations, the newborn screening process, the confirmatory testing, and treatments...

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Policy solutions to address child health equity, with evidence to support the policies, are presented. Policies address health care, direct financial support to families, nutrition, support for early childhood and brain development, ending family homelessness, making housing and neighborhoods environmentally safe, gun violence prevention, LGBTQ + health equity, and protecting immigrant children and families. Federal, state, and local policies are addressed. Recommendations of the National Academy of Science, Engineering, and Medicine and the American Academy of Pediatrics are highlighted when appropriate...

Although there has been tremendous progress toward the aspiration of delivering quality health care, among the National Academy of Medicine's (previously Institute of Medicine) six pillars of quality (health care should be safe, effective, timely, patient-centered, efficient, and equitable), the last pillar, equity, has been largely ignored. Examples of how the quality improvement (QI) process leads to improvements are numerous and must be applied to the pillar of equity related to race/ethnicity and socioeconomic status...

The climate crisis is a major public health threat for children, disproportionately affecting the most vulnerable populations. Climate change causes a myriad of health issues for children, including respiratory illness, heat stress, infectious disease, the effects of weather-related disasters, and psychological sequelae. Pediatric clinicians must identify and address these issues in the clinical setting. Strong advocacy from pediatric clinicians is needed to help prevent the worst effects of the climate crisis and to support the elimination of use of fossil fuels and enactment of climate-friendly policies...

Compared to their heterosexual and cisgender peers, sexual and gender diverse (SGD) youth, especially those from minoritized racial/ethnic groups, experience significant disparities in health, health care, and social conditions that can threaten their health and well-being. This article describes the disparities impacting SGD youth, their differential exposure to the stigma and discrimination that foster these disparities, and the protective factors that can mitigate or disrupt the impact of these exposures...