Abstract
Neurodevelopmental disorders are the most prevalent chronic medical conditions encountered in pediatric primary care. In addition to identifying appropriate descriptive diagnoses and guiding families to evidence-based treatments and supports, comprehensive care for individuals with neurodevelopmental disorders includes a search for an underlying etiologic diagnosis, primarily through a genetic evaluation. Identification of an underlying genetic etiology can inform prognosis, clarify recurrence risk, shape clinical management, and direct patients and families to condition-specific resources and supports. Here we review the utility of genetic testing in patients with neurodevelopmental disorders and describe the three major testing modalities and their yields – chromosomal microarray, exome sequencing (with/without copy number variant calling), and FMR1 CGG repeat analysis for fragile X syndrome. Given the diagnostic yield of genetic testing and the potential for clinical and personal utility, there is consensus that genetic testing should be offered to all patients with global developmental delay, intellectual disability, and/or autism spectrum disorder. Despite this recommendation, data suggest that a minority of children with autism spectrum disorder and intellectual disability have undergone genetic testing. To address this gap in care, we describe a structured but flexible approach to facilitate integration of genetic testing into clinical practice across pediatric specialties and discuss future considerations for genetic testing in neurodevelopmental disorders to prepare pediatric providers to care for patients with such diagnoses today and tomorrow.
Highlights
Studies vary in the level of phenotypic detail provided, several authors reporting on yields of CMA, ES, and FMR1 CGG repeat analysis in patients with neurodevelopmental disorders suggest that specific characteristics and additional diagnoses are associated with increased diagnostic yields [95, 111, 113, 140, 146, 198, 201, 210, 211]
Despite genetic testing yields similar to those if ID, GDD, and ASD, no formal practice guidelines regarding genetic testing for individuals with epilepsy have been published by major medical societies; various approaches to etiologic genetic testing in this patient population have been suggested by independent authors [273, 275]
Neurodevelopmental disorders are common, and a significant proportion are caused by rare copy number and exonic sequence variants of large effect size that can be identified by genetic testing
Summary
Studies vary in the level of phenotypic detail provided, several authors reporting on yields of CMA, ES, and FMR1 CGG repeat analysis in patients with neurodevelopmental disorders suggest that specific characteristics and additional diagnoses are associated with increased diagnostic yields [95, 111, 113, 140, 146, 198, 201, 210, 211]. Diagnostic yields of ES and emerging evidence that ES is cost-efficient in the etiologic evaluation of children with neurodevelopmental disorders [142, 160,161,162,163] support this assertion that ES is the most appropriate first test to pursue [65].
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