Abstract
Autism spectrum disorder (ASD) consists of a genetically heterogenous group of neurobehavioral disorders characterized by impairment in three behavioral domains including communication, social interaction, and stereotypic repetitive behaviors. ASD affects more than 1% of children in Western societies, with diagnoses on the rise due to improved recognition, screening, clinical assessment, and diagnostic testing. We reviewed the role of genetic and metabolic factors which contribute to the causation of ASD with the use of new genetic technology. Up to 40 percent of individuals with ASD are now diagnosed with genetic syndromes or have chromosomal abnormalities including small DNA deletions or duplications, single gene conditions, or gene variants and metabolic disturbances with mitochondrial dysfunction. Although the heritability estimate for ASD is between 70 and 90%, there is a lower molecular diagnostic yield than anticipated. A likely explanation may relate to multifactorial causation with etiological heterogeneity and hundreds of genes involved with a complex interplay between inheritance and environmental factors influenced by epigenetics and capabilities to identify causative genes and their variants for ASD. Behavioral and psychiatric correlates, diagnosis and genetic evaluation with testing are discussed along with psychiatric treatment approaches and pharmacogenetics for selection of medication to treat challenging behaviors or comorbidities commonly seen in ASD. We emphasize prioritizing treatment based on targeted symptoms for individuals with ASD, as treatment will vary from patient to patient based on diagnosis, comorbidities, causation, and symptom severity.
Highlights
Leo Kanner in 1943 [1] first introduced the term autism as a diagnostic label to define a specific syndrome observed in young children manifested by early onset, characteristic symptomatology, and disrupted social and emotional relationships
A study of custom-made, ultra-high-resolution microarrays reported by Ho et al [47] in 2016 were optimized for the detection of neurodevelopmental disorders (Lineagen, Salt Lake City, Utah) on 10,351 patients presenting for genetic services for neurodevelopmental disorders, Autism Spectrum Disorder (ASD), intellectual disability (ID), behavioral problems, or with or without multiple congenital anomalies (MCA) over a period of four years
The alpha-2 agonist guanfacine has been shown to be effective for attention deficit hyperactivity disorder (ADHD) in children with ASD demonstrated by a double-blind, placebo-controlled trial of guanfacine extended release in which 50% of youth on active treatment improved on the Clinical Global Impression–Improvement (CGI-I) scale [86], compared to 9.4% on placebo [87], with sedation and transient lowering of blood pressure as the most common adverse effects
Summary
Leo Kanner in 1943 [1] first introduced the term autism as a diagnostic label to define a specific syndrome observed in young children manifested by early onset, characteristic symptomatology, and disrupted social and emotional relationships. ASD affects between 1 to 2% of children in United States with a growing role for genetic factors with etiological heterogeneity. Despite the recognition of nearly 800 susceptibility, clinically relevant, or known genes for autism spectrum disorder collated by Butler et al [21] and characterized by numerous etiological studies including relevant animal models [22], it appears that no cohesive model of causation, biomarker [23], or specific mode of transmission for the development of autism has been firmly identified [24]. A list of genetic syndromes and chromosomal disorders associated with ASD is illustrated as Box 1 below. “Assessment and treatment in autism spectrum disorders: A focus on genetics and psychiatry”, Autism Research and Treatment, vol 2012, 242537, 2012 [30]
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