Epigenetics as a basis for diagnosis of neurodevelopmental disorders: challenges and opportunities

Abstract

Neurodevelopmental disorders, such as autism, are complex entities that can be caused by biological and social factors. In a subset of patients with congenital neurodevelopmental disorders, clear diagnosis can be achieved using DNA sequence-based analysis to identify changes in the DNA sequence (genetic variation). However, it has recently become clear that changes to the secondary modifications of DNA and histone structures (epigenetic variation) can also cause neurodevelopmental disorders via alteration of neural gene function. Moreover, it has recently been demonstrated that epigenetic modifications are more susceptible to alterations induced by environmental factors than are DNA sequences, and that some drugs commonly used reverse mental-stress induced alterations to histone modifications in neural genes. Therefore, application of diagnostic assays to detect epigenetic alterations will provide new insight into the characterization and treatment of neurodevelopmental disorders.

Keywords::

• diagnosis
• DNA methylation
• epigenetics
• epigenetics
• epigenome
• histone modification
• neurodevelopmental disorder
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Based on the increased number of identified neuronal genes, gene (DNA sequence)-based diagnosis has been performed. However, the number of patients with neurodevelopmental disorder who gave positive results is very limited.

• Our increase understanding of epigenetic mechanisms has enabled epigenetic (DNA modification)-based diagnosis for congenital neurodevelopmental disorders.

• Identification of transgenerational epigenetic effects opens the possibility of epigenetic-based diagnosis for acquired neurodevelopmental disorders.

• Epigenetic diagnosis for acquired neurodevelopmental disorders will allow treatment of patients with appropriate drugs and nutrition to restore the normal epigenetic status.

• Epigenome-wide association studies will enable estimation of the risk of acquired neurodevelopmental disorders, which should be of value for allocation of resource for mental health medicine.

• Advances in neuroimaging will allow real-time analysis of epigenetic abnormalities in the brain.

• Conventional genetic diagnosis and newly-designed epigenomic diagnoses, and epigenetic neuroimaging, will introduce a new era for neurodevelopmental disorder medicine.