Risk factors for autism: translating genomic discoveries into diagnostics

Abstract

Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a 'standard of care' test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.

Da invisibilidade à epidemia: a construção narrativa do autismo na mídia impressa brasileira

“…A principal delas é, sem dúvida, em relação à etiologia do transtorno. Por um lado, um número crescente de pesquisas em neurodesenvolvimento e genética vem sendo realizado em busca de um marcador biológico que contribua para a detecção precoce e o tratamento do autismo 11,12 . Por outro lado, não se pode afirmar que haja uma única causa orgânica para esse transtorno, nem que as descrições diagnósticas de manuais como o DSM e a CID sejam suficientes para esclarecer o amplo universo de suas manifestações clínicas 13 .…”

In Search of Autism Biomarkers: Possible Autism Bio-Markers Discovery at Autism Research and Treatment Center, King Saud University, KSA

“…The prevalence of autism spectrum disorder (ASD) has increased dramatically in the past few decades [3]. The current prevalence in the United States is estimated, at 1 in 91 children [4].…”

The Ever-Evolving Concept of Clinical Significance and the Potential for Sins of Omission in Genetic Research

“…Chan and colleagues and others (National Cancer Institute 2010;Scherer and Dawson 2011) have noted potential disadvantages of disclosure. Counseling and clinical testing of additional family members can be both costly and time-consuming, and can present a disincentive to consider the return of any substantial number of variants.…”

“…Distinguishing private family mutations from disease-associated variants, and determining penetrance and variable expression, in the course of family studies will lead to greater understanding of variants and thus enhanced clinical significance (Carvajal-Carmona 2010). There are currently inadequate numbers of health care providers who are specially trained to interpret and communicate this information (Scherer and Dawson 2011). The move to return selected research results could help spur further genetics training and education.…”

“…The move to return selected research results could help spur further genetics training and education. The potential for psychological harm of disclosure is often cited (Scherer and Dawson 2011), but empirical support is limited. The few existing studies (see, e.g., Ashida et al 2010;Bloss, Schork, and Topol 2011) suggest that such risks may be minimal, provided the uncertainty about the clinical expression of any variant is clearly communicated in the course of appropriate genetic counseling.…”