Advances in Genetic Diagnosis of Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental abnormalities characterized by stereotypical communicative and social impairments, affecting 1 in 88 children in the United States. Both genetic and environmental factors contribute to the etiology of ASD. Autistic traits may be part of features associated with certain syndromes or the sole clinical presentation. Due to extreme heterogeneity and variable expressivity of the condition, clinical diagnosis and management have been challenging. Major advances in genomic technologies, computing power, and bioinformatics analyses have resulted in the accelerated discovery of novel genes and risk loci associated with both inherited and sporadic forms of ASD. Pathogenic genetic defects related to ASD range from single nucleotide variation to gross chromosomal abnormalities. In this review, we first summarize the current understanding of the genetic etiology of ASD; we then discuss how genetic diagnostics may influence the management and genetic counseling of ASD; and finally, we outline the strategy to integrate genetic tests into clinical care of children with ASD. We hope to inform primary care pediatricians and clinical genetic specialists how recent advances in the genetic research of ASD have been translated into clinical genetic testing for patients.

Parents’ Perceptions of the Usefulness of Chromosomal Microarray Analysis for Children with Autism Spectrum Disorders

“…The ability to detect genetic causation for autism spectrum disorder (ASD) has improved due to the use of genome wide screening technologies such as chromosomal microarray analysis (CMA) to search for copy number variants (CNVs), and next generation sequencing for single nucleotide variation (Shen and Miller 2014; Talkowski et al 2014; Veenstra-VanderWeele et al 2004). Genetic testing is not considered a diagnostic test for ASD, however, several studies have demonstrated the clinical utility of CMA in terms of changes in clinical management and medical care (Agency for Healthcare Research and Quality (AHRQ) 2014; Beaudet 2013; Coulter et al 2011; Ellison et al 2012; Hayeems et al 2014; Henderson et al 2014; Mefford et al 2012; Riggs et al 2014; Shen et al 2010).…”

Can genetic research motivate parents to pursue genomic testing for children with autism spectrum disorder?

“…Platforms such as these are designed to share and present data from genetic testing patients among researchers [5,14,15]. Professionals involved with this project can analyze a bank of test results recorded from patients to identify previously unidentified mutated genes which may contribute to the cause of ASD and other genetic disorders [5,6]. By identifying and recording new candidate genes, the genetic causes that underlie ASD can be more accurately described and better understood [16].…”

“…Several Chromosomal disorders such as Fragile X and Down's Syndrome have also been identified as comorbid for ASD [6]. However, it is believed that roughly half of ASD genetic causes involve de novo, or non-syndromic, mutations [7].…”

“…The diagnostic yield of known ASD patients through CMA is found to be 15-20% in most studies, as well as almost 30% by prior screening on complex cases of ASD [6]. In this procedure, a blood sample is taken from the patient, and the genetic material is then comprehensively scanned in comparison to a healthy genome control [10,11].…”

Advances in Genetic Discovery and Implications for Counseling of Patients and Families with Autism Spectrum Disorders

“…Prevalence continues to increase, from ~1/88 children in 2008 to 1/68 in 2010, according to the Autism and Developmental Disabilities Monitoring Network of the Centers for Disease Control and Prevention [2, 3]. Potential reasons for the increase have been summarized elsewhere and are somewhat debatable [4•]. …”