autism and autism spectrum disorder ( asd ) are commonly used terms for a group of 
 neurodevelopmental disorder that represents social deficits , communication difficulties , 
 stereotyped or repetitive behaviors and cognitive delays1 , 2 . in general , the child with 
 autism has not exhibited same symptom , but features very different type of autism 
 characteristics . since the child with autism does not appears same or a single symptom , 
 newer term of asd has been represented as a single diagnostic category of autism 
 characteristic linking various conditions . it is known that asd reveals substantial genetic 
 variants , particularly fragile x syndrome ( fxs ) , rett syndrome , tuberous sclerosis complex 
 and structural chromosomal variations confer a high risk for asd3 . fxs is the most frequent form of inherited intellectual 
 mental retardation and commonly known as monogenic type of autism , which shows clinical 
 behavioral features such as mental retardation , learning disorder , attention deficit 
 disorder , hyperactivity disorder , anxiety and epilepsy4,5,6 . particularly , the individuals with fxs often exhibit characteristic 
 of asd or autistic behavior7 . fxs is a 
 genetic disorder that occurs by mutation of fragile x mental retardation 1 
 ( fmr1 ) gene on the x chromosome . mutation at this site is related with 
 loss of fragile x mental retardation protein ( fmrp ) that affecting physical and behavioral 
 abnormalities . the individuals with fxs also present with disturbed sleep and altered 
 circadian behavior as well . in molecular studies , the absence of fmr1 and 
 fmr2 gene induces the altered expression of clock gene related components 
 and changes circadian rhythm . in addition , clinical studies reported that sleep and 
 behavioral alteration of fxs would be associated with fmr1 and 
 fmr2 gene . as described above , asd and fxs exhibit various clinical features including mental 
 retardation and epileptic episodes4 , 6 . recently , numerous studies have focused on 
 understanding the pathophysiological mechanisms responsible for asd and fxs , and on 
 developing more effective therapeutic treatments . sairanen m et al.8 reported that asd is 
 characterized by structural defects that include a reduction in forebrain volume and 
 disruption of the neural network between the limbic system and other cerebral cortex 
 regions . in addition , recent study demonstrated that asd children presented an abnormal gait 
 compared with that of age - matched controls , they showed a reduction in cadence , gait 
 velocity , step length , and an increase in step width9 . interestingly , therapeutic physical exercise in patients with asd 
 increases hippocampal volume and promotes the robust growth of newly proliferated and/or 
 differentiated cells by increasing brain - derived neurotrophic factor ( bdnf ) in the cerebral 
 cortex10 . also , the 
 fmr1 gene was shown to play a critical role in the neural plasticity of 
 dendritic spines in studies on neuropsychological function in asd and fxs . therefore , the 
 absence of fmr1 results in dysmorphology and dendritic spine dysfunction11 , 12 . in addition , fmr1 knockout mice swim significantly slower than 
 controls and take more time to arrive at the target platform in the morris water maze13 . therapeutic physical exercise plays a 
 critical role in neuronal cell survival in asd patients , and forced aerobic exercise during 
 light photoperiods promotes vascularization and neurogenesis14,15,16 . therapeutic physical exercise facilitates the production of 
 neurotrophic factors , including nerve growth factor ( ngf ) , fibroblast growth factor-2 
 ( fgf-2 ) as well as bdnf , that improve neuropsychological function in infants with asd17 , 18 . in a previous study using the valporic acid ( 400  mg / kg)-induced asd 
 animal model , the animals with intervention of physical exercise showed incremental 
 improvement in spatial learning memory , decision making , and neurogenesis in the hippocampal 
 region via stimulating the pi3  k / akt / erk signaling pathway19 . moreover , exercise that combines physical and mental activities 
 has improved cognitive ability in individuals with asd , and participation of people with asd 
 in these activities serves the additional purpose of decreasing stereotypes20 , 21 . strikingly , a recent report suggested that a mind - body exercise 
 program could positively affect neural functional connectivity and memory processing , and 
 could therefore enhance memory function in individuals with asd22 . in a study that examined the relationship between stress and exercise , one patient with 
 autism showed abnormally high epinephrine , norepinephrine , and cortisol levels during 
 maximal and submaximal treadmill exercise compared to resting levels . even though 
 therapeutic physical exercise is somehow stressful in patient , but the subjected patient was 
 able to complete the entire protocol without experiencing any maladaptive behavior . therefore , additional studies are needed to determine the beneficial effects of therapeutic 
 physical exercise , and to provide the clinical application guideline of exercise for 
 autistic fxs patients .