Introduction
Neurodevelopmental disorder (ND) is a collective term that denotes disorders resulting in abnormal brain development at the neonatal stage and cognitive impairment. This includes both structural defects such as neural tube defects (NTDs), and neuropsychological deficits such as impairments in motor and sensory organization, delayed speech and language, difficulties in learning, and other social interactions. These impairments and defects can either be fatal and/or disabling, affecting the children’s quality of life [1].
There is a wide range of NDs detected in newborns and adults, including Attention-Deficit Hyperactivity Disorder (ADHD), autistic spectrum disorders, epilepsy, Down syndrome, Prader-Willi syndrome, schizophrenia, congenital immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, Rett syndrome, bipolar disorder, and Tourette’s syndrome [2,3]. Among these, ADHD has been shown to be the most prevalent worldwide. The global prevalence of ADHD was estimated to be 5.29% a decade ago [4]. Data from the National Survey of Children’s Health (NSCH) suggests that an estimated 9.5% of children aged 4–17 years were diagnosed with ADHD in 2007, which was further increased to 11% in 2011 in the United States [5]. A recent meta-analysis of many worldwide studies reveals that one in every 20 children is diagnosed with ADHD [6]. It is pertinent to mention that the psychological and physical impairments of most NDs take a massive toll on individuals and pose psychological and economic burdens on the family and society.
The genetic etiology for most NDs is still not clear. Although some disorders have been linked to specific mutations in single or multiple genes, there are many caused by varied factors such as genetics, epigenetics, and in–utero environment, in mothers as well as fetuses. While genomic variations such as chromosomal deletions/duplications and/or single-nucleotide mutations/polymorphisms could be either inherited or de novo in offspring, non-heritable genetic alterations are largely linked to epistatic and epigenetic alterations during development [7]. It is well established that the in–utero environment plays a vital role in embryogenesis. There are several factors such as the physiological and biochemical milieu of the maternal uterus during oocyte maturation, peri-implantation, and post-implantation stages that contribute to epigenetic alterations in the embryonic transcriptome, resulting in abnormal fetal development [8]. The placenta has also been shown to be affected by several maternal factors, leading to abnormal epigenetic regulation of various developmental genes such as LINE-1 and AluYb8, which in turn may result in neurodevelopmental disorders in the offspring [9]. During pre-term deliveries, significantly lower levels of the two most prominent neurotrophic factors, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), were detected in the placental tissue and umbilical cord plasma, suggesting plausible altered epigenetic mechanisms that could lead to altered fetal programming [10].
In view of the fact that epigenetic factors contribute to fetal development [11], it is crucial to elucidate the underlying epigenetic mechanisms playing a part in the pathophysiology of these NDs [12,13,14]. Furthermore, the epigenetic mechanisms have been shown to be altered by several factors such as lifestyle, infection, genetic and metabolic alterations, as well as other maternal factors, contributing to the neurological disorders in the offspring [15,16,17,18]. This review will bring forth a comprehensive analysis of the recent findings regarding the epigenetic landscape contributing to the pathophysiology of NDs. As epigenetic alterations are plastic and reversible in nature, potential avenues towards diagnostic and therapeutic strategies for the better management of these disorders are discussed.
References
- Banik A1, Kandilya D2, Ramya S3, Stünkel W4, Chong YS5, Dheen ST6. Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring. Genes (Basel). 2017 May 24;8(6). PMID: 28538662.