**6. Chromosomal alterations**

Numerical and structural chromosomal alterations, visible by conventional cytogenetic tech‐ niques, occur in about 6 to 7% of ASD cases and have already been described in all autoso‐ mal and sex chromosomes. These findings justify karyotyping by GTG banding as part of the etiological work-up protocol of carriers (Castermans et al., 2004; Shen et al., 2010).

Some human chromosomal aneuploidies are known to increase the risk for ASD; the most common, as identified in studies of individuals with autism, are trisomy 21 (Down syn‐ drome), monosomy of chromosome X in women (Turner syndrome), uniparental X disomy in men (Klinfelter syndrome), Y disomy and 45,X/46,XY mosaicism. Structural abnormalities include 15q11-13 duplication and deletions of 2q37, 22q11.2 and 22q13.3 (Betancour, 2011).

Due to the high number of cases that have been described and the type of genes located in them, the association of eight chromosomal regions is well established in autism including: 1q21, 7q11.23, 15q13, 15q11-13, 16p11.2, 17p11.2, 22q13.3 and 22q11.21. Rearrangements in‐ volving these regions are detected by classic cytogenetic techniques but it is recommended that more sophisticated techniques, such as array comparative genomic hybridization (ar‐ ray-CGH), are used for their evaluation (Gillberg, 1998; Griswold et al., 2012).

As expected, unbalanced changes are more frequently found in dysmorphic individuals and with delays in neuropsychomotor development due to the "extent of damage" because they result in significant gains and losses of gene content. Balanced rearrangements, however, are less frequent and can be related to mutations in DNA breakpoints. Some are so rare that it is difficult and risky to consider them a cause of autism. However, some occur at high enough frequencies to be considered risk factors for the disease. Identifying balanced changes is im‐ portant for genetic counseling, not only due to the etiologic implications, but also because these changes may predispose descendants to unbalanced rearrangements (Carter, 2011; Sherer & Dawson, 2011; Nowakowska et al., 2012).

However, chromosomic analysis detects only 3-5 megabase abnormalities. New technolo‐ gies using DNA or chromosomal microarrays can identify submicroscopic abnormalities. Microdeletions and duplications, e.g., may be identified with microarrays in individuals with ASD who previously had normal kariotype. Therefore, if cytogenetic analysis is nega‐ tive in clinically diagnosed ASD, molecular techniques are necessary.
