156 Maternal Twins and Male Gender Bias in Autism Spectrum Disorders
synthetic chemical that targets oxytocin‐ or AVP‐ receptor positive neurons
occurs at week 30 of gestation, then the neurotoxic agent will only harm a small
population of that group of neurons, resulting in partial reduction in the social
communication compartment of the brain. This hypothesis explains the concept
of the “spectrum”. It all depends on at what stage of fetal brain development a
neurotoxic agent was introduced, and what kinds of progenitor neurons it
affected, and to what degree. In the early stages, the harm to the primary pro-
genitor neurons may eliminate the whole faculty or faculties of the brain.
In exposure at later stages, the harm may be partial. Furthermore, whenever a
primary or secondary progenitor neuron is eliminated, the space left due to the
death of a particular neuron is replaced with another progenitor neuron that may
proliferate at a faster growth rate, resulting in a larger brain size, a hallmark of a
typical ASD brain. The reduction in the oxytocin‐ and AVP‐receptor positive
neurons results in damage to the areas of the brain that are generally observed in
ASD children (Table 4.1). It should be noted that brain development does not
stop at birth. The brain continues to change during the first few years of life, as
new neurotransmitters become activated and additional lines of communication
are established. Neural networks are forming and creating a foundation for pro-
cessing language, emotions, and thoughts. We will discuss the potential damag-
ing agents to this stage of brain development in the next chapter.
More than 1000 genetic and genomic disorders have been linked to ASD and
the number of genes implicated or are associated with ASD are still increasing,
yet genome‐wide association studies, CNV, and candidate gene association
have found no single genetic factor accounting for about 80% of ASD cases; the
other 20% are actual genetic diseases and should not be included in ASD.
Interestingly, trio analyses (where both the parent and the ASD child’s mRNAs
were sequenced, called exome sequencing analyses) revealed genes that have
suffered mutations only during fetal development and are not found in either
of the parents. This clearly shows that ASD is not inherited from the parents
but the new mutations are introduced during the fetal development. Hundreds
of genetic loci and more than 1000 single nucleotide and short and long genes
variants that are assumed to play a role in ASD may be the secondary outcome
of unknown synthetic chemicals that a fetus was exposed to during the prenatal
period [10,13,49]. In the attempt to collate all genes and recurrent genomic
imbalances that have been implicated in the etiology of ASD, no definite
answers have been found.De Novo Mutations
The de novo (novel, new) mutations relate to mutations that are absent in
either the biological father or the mother of an autistic child but arise during
the fetal stages of development. There are two kinds of de novo mutation: the