Fragile X Syndrome. This is an X-linked genetic disorder that is associated with autism and is characterized by unusual facial features, macro-orchidism in adulthood and cognitive impairment of variable severity. Fragile X syndrome is the most common cause of inherited mental retardation, affecting approximately 1/4,000 males and 1/8,000 females. It is caused by an increased number of trinucleotide (CGG) repeats in the FMR1 gene, which codes the fragile X mental retardation protein. Depending on the number of CGG repeats, affected alleles are classified as normal (5-40), intermediate or gray zone (~45-54), pre mutation (~55-200) or full mutation (>200). Full mutation alleles are typically associated with hypermethylation that results in gene silencing and a pathological phenotype. An important factor influencing studies of autism in FXS is that up to 90% of affected males display a variety of behavioral abnormalities that can be interpreted as atypical social interaction or autism spectrum behaviors such as perseveration, hand flapping, self-injury, avoidance of eye contact and social anxiety. Approximately 30% of individuals with FXS are within the autistic spectrum with a frequency of 7-8% FXS in populations with autism [9]. Several studies have concentrated on the differentiation between boys with both FXS and autism, and those with idiopathic autism [10,11]. The results suggest similar, although milder profiles on several measures of autistic behavior in the FXS and autism group. Tuberous Sclerosis Complex. An autosomally dominant neurocutaneous disorder, TSC arises from genetic mutations of either TSC1 on 9q or TSC2 on 16p, and is characterized by ash-leaf depigmented or other cutaneous manifestations and hamartomatous lesions in multiple organs. In the brain, the lesions or tubers are thought to cause the epilepsy seen in more than three-quarters of children with TSC [5]. Behavioral symptoms of autism are frequent in TSC. Given the frequency of epilepsy in children with TSC and the association between autism and epilepsy, it is not surprising that about 25% of patients with TSC have autism. Among patients with autism, the prevalence of TSC is 1.1-1.3%, which, although low, is 30% higher than that of TSC in the general population [5]. Rett Syndrome. This syndrome is the only ASD with a known genetic cause. It is an X-linked disorder that presents in females and is caused by mutations in the MEC2 gene [12]. Similar to autism, RS is not diagnosed until late infancy, following a period of apparently normal development. Although MECP2 mutations are rare in autism, defects in the level of the MeCP2 protein are found in brain samples of autism patients [13]. Multiple genetic and environmental factors could change the MeCP2 protein level in the brain and lead to a similar effect as the MECP2 gene mutations. Research into the role of MeCP2 in the patho genesis of RS and ASD is therefore a “Rosetta Stone” that can be used for deciphering the more complex etiology of autism in the general population [14].