Cytogenetic assays have long been used to uncover chromosomal defects in patients with autism. Cytogenetic abnormalities that have been described include 2q37 and 22q13.3 deletions and 45,X/46,XY mosaicism. Almost all chromosomes have been involved [26,27]. Cytogenetic abnormalities at the 15q11-q13 locus occur in 1-4% of patients with autism. Various population studies and case reports have described duplications, deletions, and inversions at this locus [28]. Although less than 10% of cases of autism are associated with chromosomal abnormalities, high-resolution cytogenetic scans in families with affected individuals help to locate specific genes or chromosomal regions that may be potentially associated with autism. Chromosomal Copy Number Changes in Syndromic Autism Spectrum Disorders. The introduction of array CGH has proved to be specific, sensitive and fast, and to have considerable advantages compared to other methods for the analysis of changes in DNA copy number. Array-CGH enables analysis of the whole genome in a single experiment. Although its applications have been mainly directed at detecting genomic abnormalities in cancer [29], it is suitable for analysis of DNA copy number aberrations that cause human genetic disorders [30-36]. Array-CGH combines the resolution of FISH with the whole-genome screening capacity of conventional CGH and can be applied to the detection of submicroscopic aberrations, determination of critical DNA regions of specific diseases, and elucidation of genotype-phenotype correlations [37]. Among 29 patients presenting with syndromic ASD, investigated by a DNA microarray [38], a pathogenic chromosome imbalance was detected in 27.5% of the patients. Hence, array-CGH should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. The severity of the mental retardation does not seem to be directly related to the size of the chromosomal imbalance, as the largest rearrangement was detected in the less severely retarded patients. No recurrent abnormality was found in this cohort. These results underlie the extreme genetic heterogeneity of syndromic ASD. These data strongly support the idea that only a whole-genome high-resolution analysis such as array-CGH is able to provide an accurate diagnosis for chromosomal imbalance in patients with ASD. Attention-Deficit/Hyperactivity Disorder. This is a highly heritable psychiatric disorder that affects ~4-5% of children. The syndrome persists into adulthood in about one-third of the cases and affects ~0.5-2% adults. According to the criteria of DSM-IV, diagnosis of ADHD re quires that a child meet six of nine criteria for inattention (inattentive subtype), or six of nine criteria for hyperactivity/impulsivity (hyperactive/impulsive subtype), or both (combined subtype). The behavioral problems must also have started before the age of 7 and must have persisted for at least 6 months in at least two different settings (e.g., school and home). Boys are affected three times more often than girls in the general population and 10 times more often in clinical settings. In adults, this ratio becomes 2:1 in the general population. High levels of comorbidity with other psychiatric disorders are common in both sexes. Attention deficit/hyperactivity disorder has an estimated heritability of 75-91%. The relative risk for siblings of affected children increases approximately 5-fold. Despite much research, the etiology of ADHD has still not been clarified. A genome scan was performed on 164 Dutch affected sibling pairs with ADHD [39] and has located several susceptibility loci, two of which (on chromosome regions 7p and 15q) are suggestive for linkage. The 15q region is particularly interesting, since it has also been implicated in autism and reading disability. These results may provide new directions in the search for specific genetic determinants of ADHD. In another study [40], significant linkage was found on chromosome 16p13 in a region already implicated in autism. It has been suggested that ADHD and ASD, which also have a high heritability, have common genetic factors in common. According to the DSM-IV classification, a diagnosis of ASD rules out the diagnosis of ADHD; however, a substantial number of patients with ADHD have mild problems with social interactions and communication that are rather similar to the symptoms of autism. A subgroup of autistic children also showed high levels of inattention, hyperactivity, and impulsivity. Follow-up studies suggest other regions as highly likely to harbor risk genes for ADHD: 12p13, 2q24 [41], 17p11 [42].