Other single-gene and micro deletion defects may be associated with autism. Neurofibromatosis, a common autosomal dominant disorder with neurological and cutaneous manifestations, is much less frequently associated with autism than is TSC or FXS [15]. Angelman syndrome (AS) and Prader- Willi syndrome (PWS) usually result from genetic deletions or uniparental disomy of the 15q11-q13 locus, with abnormal imprinting or genetic mutations being found in up to 5.1% of PWS cases and up to 15% of AS cases. Loss of paternally-derived genes result in PWS, whereas AS, more commonly associated with autism than PWS, can result from the loss or mutation of the maternally-derived ubiquitin protein ligase gene UBE3A or the ATP10C gene [16]. An unexpectedly large proportion of boys with Duchenne muscular dystrophy fall in the autistic spectrum [17]. Other rare single-gene defects that have been associated with autism, include those found in Sotos syndrome, Williams syndrome, hypomelanosis of Ito, Cowden syndrome, and Moebius syndrome [5]. Autism may also occur in the context of abnormal cellular metabolism, such as mitochondrial disease or dysfunction. Untreated phenylketonuria is a well-documented metabolic cause of autism; however, whether this is attributable to the resulting severe mental retardation or to the specific defi- cit in the dopamine pathway, is uncertain [18]. A clinic-based study [19] reports high levels of uric acid secretion in up to one-quarter of patients with autism and amelioration of certain symptoms with anti hyperuricosuric therapy. This represents a significant proportion of these clinical samples, but the result has not been widely replicated and the factors that are responsible for this type of “purine autism” remain to be identified. Avdjieva-Tzavella D have been associated with autism, include those found in Sotos syndrome, Williams syndrome, hypomelanosis of Ito, Cowden syndrome, and Moebius Autism may also occur in the context of abnormal cellular metabolism, such as mitochondrial disease or dysfunction. Untreated phenylketonuria is a well-documented metabolic cause of autism; however, whether this is attributable to the resulting severe mental retardation or to the specific defi- cit in the dopamine pathway, is uncertain [18]. A clinic-based study [19] reports high levels of uric acid secretion in up to one-quarter of patients with autism and amelioration of certain symptoms with anti hyperuricosuric therapy. This represents a significant proportion of these clinical samples, but the result has not been widely replicated and the factors that are responsible for this type of “purine autism” Studies of twins [20,21] have reported 60% concordance for classic autism in monozygotic (MZ) twins vs. 0% in dizygotic (DZ) twins, the higher MZ concordance attesting to genetic inheritance as the predominant causative agent. Reevaluation for a broader autistic phenotype that included communication and social disorders, in creased concordance remarkably from 60 to 92% in MZ twins and from 0 to 10% in DZ pairs. This suggests that interactions between multiple genes cause “idiopathic” autism but that epigenetic factors and exposure to environmental modifiers may contribute to variable expressions of autism-related traits. The risk for developing autism in siblings of affected individuals is 75-fold greater than in the general population [5]. Evidence from studies of twins, familial aggregation, and rare chromosomal abnormalities provide a compelling argument for some substantive heritable component in ASD etiology. However, no specific genes have been implicated.