**7. Cytogenetics and chromosomes 15q and 7q**

Cytogenetic assays used for decades to explore chromosomal defects in patients with autism, and a number of cytogenetic abnormalities besides fragile X have been described [9].

Less than 10% of cases of autism are associated with clear chromosomal abnormalities, Cytogenetic abnormalities found at the 15q11-q13 locus are reported most frequently in patients with autism, up to 1–4%.

Analysts have started to look at the glutamatergic framework within the pathogenesis of autism. A few lines of prove recommend the inclusion of glutamate receptors: (1) Indications of hypoglutamatergia mirror the behavioral phenotypes of autism. (2) Serotonin receptor 2A (5-HT2A) agonists cause behavior comparative to autism, maybe through expression of 5HT2A on glutamatergic-inhibiting GABAergic neurons. (3) Association studies have involved the inclusion of GABAA receptors on 15q11-q13 that in turn balance glutamatergic function. (4) Excessive glutamatergic activity is associated with epileptiform activity, which is highly associated with autism.

The inotropic glutamate receptor 6 (GluR6) gene on chromosome 6q21 was associated significantly with autism. Also, the metabotropic glutamate receptor GRM8 in the chromosome 7q31-q33 autism susceptibility locus has exhibited linkage disequilibrium LD with autism. These data highlight the need for additional investigations into the relationship between the glutamate system and autism.

The neuromodulator oxytocin (OT) is also potentially relevant to the impaired sociability of autism [9].

Autism genes have been troublesome to recognize, in spite of the fact that well known the high heritability of autism disorders. Up to 10% of autism cases may be due to uncommon sequence and gene dosage variations, for example, mutations in NRXN1, NLGN3/4X, SHANK3, and copy number variants at 15q11-q13 and 16p11.2 [10].

A number of illnesses of known etiology, including Rett disorder, fragile X disorder, neurofibromatosis, tuberous sclerosis, Potocki-Lupski syndrome and Smith-Lemli-Opitz syndrome, are also related with autism. The remaining 90% of autism spectrum disorders, whereas exceedingly familial, have unknown hereditary etiology [10].

## **8. Genes implicated in autism and epilepsy**

The genetic abnormalities in autism and epilepsy not completely identified.

Cytogenetic studies have identified recurrent, maternally inherited duplications of chromosome 15q11-13 along with other rare chromosomal abnormalities is considered to be an important cause of ASD [8].

Some genes, such as NLGN4, NRXN1, and SHANK3, have been identified by array-based methods. Although they collectively account for an estimated 15% of cases, variants at these and other loci are detected in no more than 1–2% of children with an ASD [8].

In addition to that copy number variants (CNVs; e.g., microdeletions, microduplications, insertions) and single gene disorders have been found to be associated to ASD.

Many disease genes have been described as related to ASD, for example: SCN 1A, SCN2A, KCNMA1, NLGN4X, NRXN1, SYNGAP1, ARX, SHANK3, CNTNAP2, NLGN4X, and play important role in epilepsy [11].

#### **9. Genetic syndromes with ASD and epilepsy**

Gene disorders known to be associated with ASD, such as Rett Syndrome (MECP2Fragile X Syndrome (FMR1), 22q13 Deletion Syndrome/Phelan-McDermid Syndrome,), and Tuberous Sclerosis (TSC1, TSC2), and cortical dysplasia focal epilepsy syndrome (CDFE) a recessive nonsense mutation in CNTNAP2 are associated with epilepsy [12].

CNTNAP2 (also known as CASPR2) encodes a neuronal transmembrane protein member of the neurexin superfamily involved in neuron-glia interactions and clustering of K+ channels in myelinated axons. This is supported by the imaging and pathology data in patients with CDFE, in whom nearly half manifest presumed neuronal migration abnormalities on MRI, confirmed by histological analysis of brain tissue resected from patients who underwent surgery for epilepsy.

It is rare disorder resulting in epileptic seizures, language regression, intellectual disability, hyperactivity, and, in nearly two-thirds of the patients, autism [13].

The Continuous Spikes and Waves during Slow-wave Sleep syndrome (CSWSS) and Landau-Kleffner (LKS) syndrome are two epileptic encephalopathies that share common clinical features, including seizures and regression with autistic features. Both LKS and Regressive ASD patients experience an onset of regression. In LKS, the regression is specific to language skills but in Regressive ASD, it is a global. The important difference between both, the age of onset of regression for LKS is between the ages of 3 and 9 years, whereas for Regressive ASD the onset is before 2 years of age.

#### **10. The autism-epilepsy phenotype**

The characteristics of the autism-epilepsy phenotype propose that there are fundamental etiologies and pathologies dependable for both the seizures and the sociocognitive and communicative behaviors that characterize autism. Understanding of neuronal systems and the part of cellular dysfunction, and molecular derangements common to both autism and epilepsy.

#### **10.1 Neural networks in epilepsy and autism**

Both epilepsy and autism may be consequences of disorders of large-scale neural networks with alterations in cortical-subcortical systems connectivity.

*Review in Autism and Epilepsy DOI: http://dx.doi.org/10.5772/intechopen.93424*

Alterations in subcortical systems such as basal ganglia-substantia nigra connectivity, may lower the seizure threshold, contribute to cognitive impairments and to the motor stereotypies commonly found in autism.

A disorder in which abnormalities of interneurons are hypothesized and in which both autism and epilepsy commonly coexist is infantile spasm [14].

Malformations of cortical development (MCD), due to focal disruption of normal cortical organization are commonly lead to epilepsy, which also can lead to autism, as is highlighted in tuberous sclerosis in which both autism and epilepsy co-exist [14].

#### **10.2 Biomarker for autism gives hope for future autism treatment**

The clinical heterogeneity and molecular complexities of autism spectrum disorders have increasing interest into biomarkers and endophenotypes, measurable quantitative parameters able to facilitate more reliable diagnoses and may help in the treatment of ASD.

'Biomarkers' can be defined as biological variable or cellular alteration associated with the disease and measurable directly using sensitive and reliable quantitative procedures [15].

Elevated blood serotonin (5-HT) levels, and serotonin transporter (SERT) consistently recorded in individuals with ASD [16].

#### **11. Conclusions**

The progression of biomarker research in autism mirrors that of other neurologic disorders in that it is still in its infancy and marked largely by discovery rather than validation.

The search for biomarkers for autism will proceed, given the profundity and extend of their potential benefits for individuals with autism and their families. If effective, biomarkers for autism may one day demonstrate important for finding out chance, helping with determination and/or recognizing therapeutic interventions.

Finally, Biomarker research has great heuristic potential in targeting autism diagnosis and treatment.
