Fragile X Syndrome (Mini scriptie, Psychobiologie)
Is the generalisation of idiopathic autism and
Fragile X syndrome a mistake?
Abstract
Autism is a congenital pervasive developmental disorder. There are two kinds of autism; idiopathic autism and secondary autism. Secondary autism is autism in which a known environmental agent, chromosome abnormality or single-gene disorder can be identified. In contrast, the main cause of idiopathic autism is unknown. Fragile X syndrome is a case of secondary autism. People nowadays often treat patients with Fragile X the same as patients with idiopathic autism. Sharing a lot of features and considering the fact that Fragile X can also come with autism makes it interesting to compare the two disorders. This leads us to the question; what is the difference between patients diagnosed with idiopathic autism and patients diagnosed with Fragile X syndrome? This review discusses the genetic, phenotypic and behavioural differences between the two disorders. The biggest dissimilarity must be the fact that Fragile X is caused by a single-gene mutation and idiopathic autism is caused by more, and some of them, unknown mutations in the human brain. Differences are found between the neurobiological phenotypic features and concerning the communication skills and the social profiles of the two disorders. Fragile X patients appear to be less impaired then patients with idiopathic autism. By explaining the differences between the two disorders, this review shows an insight in why the generalisation is unseemly. It can be determined that the two disorders are different and that they should be treated differently. Taking this conclusion seriously may help researchers to develop future studies and create more awareness and certainty about the differences between the disorders.
Introduction
Autism is a congenital pervasive developmental disorder. Patients often have deficits in social interactions, (non-)verbal communication and aberrant repetitive behaviour, including self-injury. Most of the symptoms appear during the first three years of life. Patients get diagnosed with autism on basis of certain behavioural criteria and questionnaires (Hall et al. 2010). There are two kinds of autism; idiopathic and secondary autism. The main cause underlying idiopathic autism (IA) is unknown. Studies suggest the autism phenotype cannot be attributed to a single-gene (Zhang et al. 2009). Secondary autism is autism in which a known environmental agent, chromosome abnormality, or single-gene disorder can be identified. The genetic cause of secondary autism often involves X chromosomes. Fragile X syndrome (FXS) is both a kind of secondary autism and an intellectual disability. Intellectual disability can be defined as a failure to develop a sufficient adaptive and cognitive level. The first association made between autism and FXS was in 1982 by Brown and Meryash (Wilson et al. 2009). FXS is mostly reflected in maturation, learning or social adjustment. Fragile X syndrome causes about 20% of all the X linked intellectual disability cases. It is the most widespread inherited cause of single gene Fragile X Retardation 1 (FMR1). It has a huge effect on the individuals and their families. FXS patients often show autistic like behaviour as well as distinct physical phenotypic features such as a large prominent forehead. The prevalence of idiopathic autism is estimated to be 1 in 152 children. By contrast the prevalence of Fragile X is estimated to be 1 in 2500 to 1 in 3600. (Wilson et al. 2009). Not every patient with FXS fulfils all the criteria for autism. In five studies with a total of 193 participants with FXS, researchers found autism ranging from 0 to 33% (Demark et al. 2003). This means that not every individual with Fragile X is diagnosed with autism, although the disorder is classified by the name ‘secondary autism’. Interestingly, FXS and IA share a lot of the behavioural phenotype features. Sharing these features and considering the fact that FXS can also come with autism makes it interesting to compare the two disorders (Fahim et al. 2012). There is more known about the pathology of FXS in comparison to IA and FXS is therefore easier to modulate. For example, comparing the two disorders is hoped to shed light on common aetiological mechanisms in both disorders (Hall et al. 2010). This leads us to the question; what is the difference between patients diagnosed with IA and patients diagnosed with Fragile X syndrome? This review discusses some of the known differences between the two disorders to show an insight in whether this classification is appropriate or not. This will avoid generalisation and makes it more easy to come with effective interventions which can contribute and treat intellectual disabled and autistic patients in the future. The next 3 chapters review the genetic, phenotypic and behavioural differences between patients with FXS and idiopathic autism.
Abstract
Autism is a congenital pervasive developmental disorder. There are two kinds of autism; idiopathic autism and secondary autism. Secondary autism is autism in which a known environmental agent, chromosome abnormality or single-gene disorder can be identified. In contrast, the main cause of idiopathic autism is unknown. Fragile X syndrome is a case of secondary autism. People nowadays often treat patients with Fragile X the same as patients with idiopathic autism. Sharing a lot of features and considering the fact that Fragile X can also come with autism makes it interesting to compare the two disorders. This leads us to the question; what is the difference between patients diagnosed with idiopathic autism and patients diagnosed with Fragile X syndrome? This review discusses the genetic, phenotypic and behavioural differences between the two disorders. The biggest dissimilarity must be the fact that Fragile X is caused by a single-gene mutation and idiopathic autism is caused by more, and some of them, unknown mutations in the human brain. Differences are found between the neurobiological phenotypic features and concerning the communication skills and the social profiles of the two disorders. Fragile X patients appear to be less impaired then patients with idiopathic autism. By explaining the differences between the two disorders, this review shows an insight in why the generalisation is unseemly. It can be determined that the two disorders are different and that they should be treated differently. Taking this conclusion seriously may help researchers to develop future studies and create more awareness and certainty about the differences between the disorders.
Introduction
Autism is a congenital pervasive developmental disorder. Patients often have deficits in social interactions, (non-)verbal communication and aberrant repetitive behaviour, including self-injury. Most of the symptoms appear during the first three years of life. Patients get diagnosed with autism on basis of certain behavioural criteria and questionnaires (Hall et al. 2010). There are two kinds of autism; idiopathic and secondary autism. The main cause underlying idiopathic autism (IA) is unknown. Studies suggest the autism phenotype cannot be attributed to a single-gene (Zhang et al. 2009). Secondary autism is autism in which a known environmental agent, chromosome abnormality, or single-gene disorder can be identified. The genetic cause of secondary autism often involves X chromosomes. Fragile X syndrome (FXS) is both a kind of secondary autism and an intellectual disability. Intellectual disability can be defined as a failure to develop a sufficient adaptive and cognitive level. The first association made between autism and FXS was in 1982 by Brown and Meryash (Wilson et al. 2009). FXS is mostly reflected in maturation, learning or social adjustment. Fragile X syndrome causes about 20% of all the X linked intellectual disability cases. It is the most widespread inherited cause of single gene Fragile X Retardation 1 (FMR1). It has a huge effect on the individuals and their families. FXS patients often show autistic like behaviour as well as distinct physical phenotypic features such as a large prominent forehead. The prevalence of idiopathic autism is estimated to be 1 in 152 children. By contrast the prevalence of Fragile X is estimated to be 1 in 2500 to 1 in 3600. (Wilson et al. 2009). Not every patient with FXS fulfils all the criteria for autism. In five studies with a total of 193 participants with FXS, researchers found autism ranging from 0 to 33% (Demark et al. 2003). This means that not every individual with Fragile X is diagnosed with autism, although the disorder is classified by the name ‘secondary autism’. Interestingly, FXS and IA share a lot of the behavioural phenotype features. Sharing these features and considering the fact that FXS can also come with autism makes it interesting to compare the two disorders (Fahim et al. 2012). There is more known about the pathology of FXS in comparison to IA and FXS is therefore easier to modulate. For example, comparing the two disorders is hoped to shed light on common aetiological mechanisms in both disorders (Hall et al. 2010). This leads us to the question; what is the difference between patients diagnosed with IA and patients diagnosed with Fragile X syndrome? This review discusses some of the known differences between the two disorders to show an insight in whether this classification is appropriate or not. This will avoid generalisation and makes it more easy to come with effective interventions which can contribute and treat intellectual disabled and autistic patients in the future. The next 3 chapters review the genetic, phenotypic and behavioural differences between patients with FXS and idiopathic autism.
Unlike idiopathic autism, Fragile X syndrome
relies on a single gene
There are multiple genetic differences between IA and FXS. To understand these differences this chapter first discusses some of the known genetic causes of autism and FXS. The mutations in IA involve alleles at multiple loci and interactions with environmental factors. Thereby IA has an unusual sex ratio, clinical variation within families and low recurrent risk to siblings. These factors do not rely on a single gene model like FXS. Autism is an entirely behavioural diagnosis and has no largely understood aetiologies (Demark et al. 2003). Investigating an autistic phenotype which included communication and social disorders increased concordance from 60% to 92% in monozygotic twins and from 0% to 10% in dizygotic twins. This suggests that idiopathic autism is caused by multiple interactions between multiple genes but epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The number and identity of genes involved is largely unknown (Muhle et al. 2004). The genetic aetiology of FXS has been more clearly. It is an X linked dominant disorder caused by a mutation in a single gene fragile X mental retardation 1 (FMR1). Patients show an expansion of a trinucleotide repeat in the FMR1 gene on the X chromosome. This trinucleotide contains ones the cytosine amino acid and twice the guanine amino acid (CGG). The CGG nucleotide repeats itself hundreds or thousands of times while in a general population the FMR1 gene contains 6 to 50 repeats (Demark et al. 2003). This eventually leads to silencing the gene. When having a premutation the CGG nucleotide repeats itself 55 to 200 times. Carriers of this premutation are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats). Yet they can develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction (Hagerman & Hagerman 2015). Generally, the FMR1 gene makes a product called the fragile X mental retardation protein (FMRP). This protein is an RNA binding and carrier protein. Its job is to chaperone the mRNAs produced from many other genes to the synapse. Normally FMRP regulates the translation of these mRNAs into proteins that are important for synapse formation and plasticity. There are multiple theories about how FRMP regulates this translation repression but the precise mechanism is unknown (Delsa Dean et al. 2016).
As told earlier this paragraph idiopathic autism is not due to a single gene mutation. The syndrome results from multiple genes interacting together. That is why previous studies examined various candidate genes, including; WNT2, MECP2 and FMRP. The WNT family of genes has a big part in the development of numerous organs and organ systems. WNT2 is also adjacent to a chromosomal breakpoint in individuals with autism and is located in the region of chromosome 7q31-33. Chromosome 7q31-33 is known to be linked with autism. Remarkable is that the autism phenotype is also associated with mutations in FMR1. As discussed earlier mutations in FMR1 are the underlying abnormalities in FXS. Mutations in MECP2 is the genetic basis for Rett syndrome. Rett syndrome is a severe neurodevelopmental disease and leads to mental and physical disabilities. It affects mostly females. Although this syndrome rarely causes autism, MECP2 expression defects were previously found in autism brain. Zhang et al. (2009) examined the expression levels of these autism-associated genes (FMR1, WNT2, MECP2) in various brain regions of fragile X mice. The results showed a drastic and significant reduction of FMR1 mRNA in the hippocampus, cortex, cerebellum, diencephalons and brainstem in the Fragile X KO mice in comparison to the wildtype (WT) level. MECP2 mRNA expression in fragile X brain regions, as compared to the wildtype level, was increased in all brain regions except the cerebellum, showing a significant difference between the cerebellum and each of the four other regions. When looking at the WNT2 expression the comparison of KO/WT ratios showed a significant difference between the brainstem and each of the four other regions. FXS and autism differ at the level of single-gene dysfunction. Yet they may bear a great deal of similarities in terms of network dysfunctions and combination effects of genetic, epigenetic and environmental modifying factors on these network dysfunctions (Zhang et al. 2009). The deficiency of FMRP therefore may influence the expression of many other genes which may be related to autism. This also includes WNT2 and MECP2 proteins.
In conclusion, there is some behavioural overlap between the two genetic mechanisms. It has been suggested that the lack of FMRP produces changes in the translation of other proteins in the brain that are associated with autism. Yet the biggest discussed dissimilarity in this chapter must be the fact that FXS is caused by a single-gene mutation and IA is caused by more, and some of them, unknown mutations in the human brain. Also, epigenetic factors and exposure to environmental modifiers may contribute to variable expression of IA related traits.
There are multiple genetic differences between IA and FXS. To understand these differences this chapter first discusses some of the known genetic causes of autism and FXS. The mutations in IA involve alleles at multiple loci and interactions with environmental factors. Thereby IA has an unusual sex ratio, clinical variation within families and low recurrent risk to siblings. These factors do not rely on a single gene model like FXS. Autism is an entirely behavioural diagnosis and has no largely understood aetiologies (Demark et al. 2003). Investigating an autistic phenotype which included communication and social disorders increased concordance from 60% to 92% in monozygotic twins and from 0% to 10% in dizygotic twins. This suggests that idiopathic autism is caused by multiple interactions between multiple genes but epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The number and identity of genes involved is largely unknown (Muhle et al. 2004). The genetic aetiology of FXS has been more clearly. It is an X linked dominant disorder caused by a mutation in a single gene fragile X mental retardation 1 (FMR1). Patients show an expansion of a trinucleotide repeat in the FMR1 gene on the X chromosome. This trinucleotide contains ones the cytosine amino acid and twice the guanine amino acid (CGG). The CGG nucleotide repeats itself hundreds or thousands of times while in a general population the FMR1 gene contains 6 to 50 repeats (Demark et al. 2003). This eventually leads to silencing the gene. When having a premutation the CGG nucleotide repeats itself 55 to 200 times. Carriers of this premutation are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats). Yet they can develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction (Hagerman & Hagerman 2015). Generally, the FMR1 gene makes a product called the fragile X mental retardation protein (FMRP). This protein is an RNA binding and carrier protein. Its job is to chaperone the mRNAs produced from many other genes to the synapse. Normally FMRP regulates the translation of these mRNAs into proteins that are important for synapse formation and plasticity. There are multiple theories about how FRMP regulates this translation repression but the precise mechanism is unknown (Delsa Dean et al. 2016).
As told earlier this paragraph idiopathic autism is not due to a single gene mutation. The syndrome results from multiple genes interacting together. That is why previous studies examined various candidate genes, including; WNT2, MECP2 and FMRP. The WNT family of genes has a big part in the development of numerous organs and organ systems. WNT2 is also adjacent to a chromosomal breakpoint in individuals with autism and is located in the region of chromosome 7q31-33. Chromosome 7q31-33 is known to be linked with autism. Remarkable is that the autism phenotype is also associated with mutations in FMR1. As discussed earlier mutations in FMR1 are the underlying abnormalities in FXS. Mutations in MECP2 is the genetic basis for Rett syndrome. Rett syndrome is a severe neurodevelopmental disease and leads to mental and physical disabilities. It affects mostly females. Although this syndrome rarely causes autism, MECP2 expression defects were previously found in autism brain. Zhang et al. (2009) examined the expression levels of these autism-associated genes (FMR1, WNT2, MECP2) in various brain regions of fragile X mice. The results showed a drastic and significant reduction of FMR1 mRNA in the hippocampus, cortex, cerebellum, diencephalons and brainstem in the Fragile X KO mice in comparison to the wildtype (WT) level. MECP2 mRNA expression in fragile X brain regions, as compared to the wildtype level, was increased in all brain regions except the cerebellum, showing a significant difference between the cerebellum and each of the four other regions. When looking at the WNT2 expression the comparison of KO/WT ratios showed a significant difference between the brainstem and each of the four other regions. FXS and autism differ at the level of single-gene dysfunction. Yet they may bear a great deal of similarities in terms of network dysfunctions and combination effects of genetic, epigenetic and environmental modifying factors on these network dysfunctions (Zhang et al. 2009). The deficiency of FMRP therefore may influence the expression of many other genes which may be related to autism. This also includes WNT2 and MECP2 proteins.
In conclusion, there is some behavioural overlap between the two genetic mechanisms. It has been suggested that the lack of FMRP produces changes in the translation of other proteins in the brain that are associated with autism. Yet the biggest discussed dissimilarity in this chapter must be the fact that FXS is caused by a single-gene mutation and IA is caused by more, and some of them, unknown mutations in the human brain. Also, epigenetic factors and exposure to environmental modifiers may contribute to variable expression of IA related traits.
White and grey matter differences between
Fragile X and idiopathic autism
In this chapter the phenotypic differences between IA and FXS are reviewed. For a disorder with such a big impact on the life of an individual, the brain of a patient with FXS or IA, at least at a superficial level, looks relatively normal. (REFERENTIE NAAR KANDEL). The most consistent neurobiological findings of IA are an enlarged head circumference and an enlarged brain volume, also called macrocephaly and macroencephaly (Fahim et al. 2012). Sharing a lot of features makes it interesting to examine the brain matters of patients with FXS and idiopathic autism and see if they also share the same neurobiological phenotypic features. Fahim et al. (2012) examined the neuroanatomy of the autistic phenotype and reported an increased total and regional grey matter (GM) and white matter (WM) brain volume in individuals with idiopathic autism and individuals with FXS relative to normal controls and patients with Williams syndrome. The reason for adding a Williams syndrome group stems from the fact that phenotypically and genetically Williams syndrome is different from IA and FXS, which are very phenotypically associated. They used an MRI to analyse the different brain matter. It is considerable that this excess suggests reduced regression of neuronal processes, like neuronal pruning, in cortical and subcortical regions in FXS and IA. This can be due to mutations in the FMR1 gene or other candidate genes involved with autism and FXS. (Fahim et al. 2012). There is no difference found in the neurobiological phenotype between FXS and IA (Fahim et al. 2012). Wilson et al. (2009) examined GM differences between patients with FXS and idiopathic autism. Inclusion in the IA group also required that individuals tested negative for FXS. They used voxel-based morphometry (VBM) and MRI to compare regional GM volumes across the whole brain. Multiple brain regions were found to have GM differences between the FXS and IA group. Increases in grey matter in the individuals with IA relative to FXS are observed in the left inferior frontal gyrus, the left middle frontal gyrus, and the right inferior temporal gyrus. Increased grey matter volume in individuals with FXS relative to individuals with IA are observed in the left middle and superior frontal gyri, the left postcentral gyrus, the left inferior, middle, and superior temporal gyri, the right superior temporal gyrus, the right parahippocampal gyrus, the left and right cingulate body; the left anterior cingulate gyrus, the left and right caudate nuclei, and the left and right cerebellum (Wilson et al. 2009). Hall et al. (2016) investigated profiles of aberrant white matter microstructure in Fragile X syndrome. This study did not compare the brain structures with individuals with IA, but with healthy participants. Studies in which patients with FXS are compared with neurotypical controls, it is unclear whether the differences in WM microstructure are specific to FXS. It is possible that the differences are due to differences in IQ or other cognitive and behavioural symptoms between the groups. That is why the participants in this research were matched on age, IQ and degree of autistic symptoms. Group differences were found in the Left inferior longitudinal fasciculus (ILF), right ILF, uncinate fasciculus and cingulate hippocampus. The findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus. This is most likely caused by inefficient synaptic pruning as a result of decreased or absent FMRP. (Hall et al. 2016)
Taking the results of the researches in this chapter together it is most likely that there is a difference between the neurobiological phenotypic features in idiopathic autism and FXS. Patients with Fragile X syndrome have a decreased amount of FMRP. Normally FMRP regulates the translation of these mRNAs into proteins that are important for synapse formation and plasticity. The absence of FMRP can result in inefficient synaptic pruning. This can result in abnormal WM and GM structure in the human brain. Why Wilson et al. (2009) found differences between the two disorders and Fahim et al. (2012) did not, can be due to the fact that Wilson et al. (2009) made sure that the participants with autism had no FXS. It is unclear if Fahim et al. (2012) did the same. If they did not, this can be an important cause of the difference between the two researches.
In this chapter the phenotypic differences between IA and FXS are reviewed. For a disorder with such a big impact on the life of an individual, the brain of a patient with FXS or IA, at least at a superficial level, looks relatively normal. (REFERENTIE NAAR KANDEL). The most consistent neurobiological findings of IA are an enlarged head circumference and an enlarged brain volume, also called macrocephaly and macroencephaly (Fahim et al. 2012). Sharing a lot of features makes it interesting to examine the brain matters of patients with FXS and idiopathic autism and see if they also share the same neurobiological phenotypic features. Fahim et al. (2012) examined the neuroanatomy of the autistic phenotype and reported an increased total and regional grey matter (GM) and white matter (WM) brain volume in individuals with idiopathic autism and individuals with FXS relative to normal controls and patients with Williams syndrome. The reason for adding a Williams syndrome group stems from the fact that phenotypically and genetically Williams syndrome is different from IA and FXS, which are very phenotypically associated. They used an MRI to analyse the different brain matter. It is considerable that this excess suggests reduced regression of neuronal processes, like neuronal pruning, in cortical and subcortical regions in FXS and IA. This can be due to mutations in the FMR1 gene or other candidate genes involved with autism and FXS. (Fahim et al. 2012). There is no difference found in the neurobiological phenotype between FXS and IA (Fahim et al. 2012). Wilson et al. (2009) examined GM differences between patients with FXS and idiopathic autism. Inclusion in the IA group also required that individuals tested negative for FXS. They used voxel-based morphometry (VBM) and MRI to compare regional GM volumes across the whole brain. Multiple brain regions were found to have GM differences between the FXS and IA group. Increases in grey matter in the individuals with IA relative to FXS are observed in the left inferior frontal gyrus, the left middle frontal gyrus, and the right inferior temporal gyrus. Increased grey matter volume in individuals with FXS relative to individuals with IA are observed in the left middle and superior frontal gyri, the left postcentral gyrus, the left inferior, middle, and superior temporal gyri, the right superior temporal gyrus, the right parahippocampal gyrus, the left and right cingulate body; the left anterior cingulate gyrus, the left and right caudate nuclei, and the left and right cerebellum (Wilson et al. 2009). Hall et al. (2016) investigated profiles of aberrant white matter microstructure in Fragile X syndrome. This study did not compare the brain structures with individuals with IA, but with healthy participants. Studies in which patients with FXS are compared with neurotypical controls, it is unclear whether the differences in WM microstructure are specific to FXS. It is possible that the differences are due to differences in IQ or other cognitive and behavioural symptoms between the groups. That is why the participants in this research were matched on age, IQ and degree of autistic symptoms. Group differences were found in the Left inferior longitudinal fasciculus (ILF), right ILF, uncinate fasciculus and cingulate hippocampus. The findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus. This is most likely caused by inefficient synaptic pruning as a result of decreased or absent FMRP. (Hall et al. 2016)
Taking the results of the researches in this chapter together it is most likely that there is a difference between the neurobiological phenotypic features in idiopathic autism and FXS. Patients with Fragile X syndrome have a decreased amount of FMRP. Normally FMRP regulates the translation of these mRNAs into proteins that are important for synapse formation and plasticity. The absence of FMRP can result in inefficient synaptic pruning. This can result in abnormal WM and GM structure in the human brain. Why Wilson et al. (2009) found differences between the two disorders and Fahim et al. (2012) did not, can be due to the fact that Wilson et al. (2009) made sure that the participants with autism had no FXS. It is unclear if Fahim et al. (2012) did the same. If they did not, this can be an important cause of the difference between the two researches.
Better communication and social skills in Fragile X in comparison to idiopathic autism
A lot of previous researchers have found autistic behavioural features in patients with Fragile X syndrome. As told earlier there is a major generalisation when it comes to FXS and IA; often individuals with FXS and individuals with IA are treated the same. This chapter discusses some of the behavioural differences between the two disorders. Males with Fragile X of all intellectual levels generally have attentional problems and are hyperactive during childhood. Patients with FXS are known to be more shy and less sociable than are individuals without the syndrome (Demark et al. 2003). Children with FXS showed less gaze avoidance when interacting with their mothers than when interacting with strangers, whereas children with IA showed similar levels of gaze avoidance with both familiar and unfamiliar persons (Hall et al. 2010). There are considerable behavioural features among individuals with IA. The diagnostic criteria for IA are impaired social skills; delayed or non-existent communication abilities, and stereotypic, repetitive behaviours (Demark et al. 2003). Demark et al. (2003) compared children with IA to children with FXS on the Childhood Autism Rating Scale and the Reiss Scales for Children’s Dual Diagnosis. They used a well-researched behavioural rating scale; the Childhood Autism Rating Scale (CARS), which helps determine the degree of autistic behaviours present in children with Fragile X. They found that 47% of the children with Fragile X who scored above the CARS cut-off (Fragile X–autism group) were more impaired than the remaining children (Fragile X–no autism) on CARS subscales related to emotion, visual and listening responses, and communication. The autism group’s Reiss scores were higher than Fragile X–no autism group, but not Fragile X–autism group. Although the Childhood Autism Rating Scale identified almost 50% of children with Fragile X as having autism, qualitative differences may exist in specific autistic-like behaviours between children with autism and children with Fragile X (Demark et al. 2003). Hall et al. (2010) examined the profiles of autistic behaviours shown by boys and girls with FXS, using the Social Communication Questionnaire (SCQ) and the Autism Diagnostic Observation Schedule (ADOS). ADOS is a semi-structured observational measure of autistic behaviour administered directly to the participant by a trained researcher or clinician. SCQ is a 40-item checklist of autistic behaviours. Taken the data of previous research together, they determined that although individuals with FXS exhibit high levels of social avoidance and repetitive behaviours and language, their reciprocal social interaction skills and communication skills may be qualitatively less impaired than in some samples of individuals diagnosed with idiopathic autism. These data suggest that there are significant differences in behaviour between FXS and IA.
Given these differences, the implementation of standard autism interventions for individuals with FXS may not be optimal (Hall et al. 2010). The overarching differences are found concerning the communication skills and the social profiles of the two disorders. FXS patients appear to be less impaired then patients with IA. Yet it is hard to determine the exact behavioural features because of the different versions of IA and FXS. The researches discussed in this chapter suggest that there is a difference between FXS with autism and FXS without autism. Just a little research is done when it comes to comparing these two kinds of Fragile X.
Discussion
There has been a major generalisation when it comes to Fragile X and idiopathic autism. This review shows different sides of the two disorders and the fact that there is not just one factor relevant discussing them. Discussing the genetics, phenotype and behaviour of the two disorders this review is meant to shed a light on both FXS an IA. FXS is caused by a mutation in a single gene; the FMR1 gene. The number and identity of genes involved in IA is largely unknown. Also, epigenetic factors and exposure to environmental modifiers may contribute to variable expression of IA related traits. Phenotypic research showed white matter and grey matter differences between FXS and IA brains. This may be due to the lack of FMRP in FXS brains. FMRP regulates the translation of certain mRNAs that are important for synapse formation and plasticity. Reviewing the behaviour of the two disorders, reciprocal social interaction skills and communication skills are found to be qualitatively less impaired in individuals with FXS than in individuals diagnosed with idiopathic autism. Taking the outcome of the reviewed researches together most studies show a significant difference between the two disorders.
However, it can be determined that there are multiple factors relevant discussing the differences; there are genetic, phenotypic and behavioural differences. Most researches are done examine FXS and idiopathic autism while FXS has many different symptoms and does not always come with autism. It is uncertain whether all the measures are done by participants which are diagnosed with FXS and no autism or not. This may contribute to the outcome in several researches.
By explaining the differences between FXS and IA this review shows an insight in why this generalisation is unseemly. It can be determined that the two disorders are different and that they should be treated differently. Yet, at the present time, there is no accepted therapeutic strategy to treat the core symptoms of idiopathic autism (Zhang et al. 2009). This review can help future investigators to not make the category mistake by classifying both FXS and IA with the same ‘autism’. There is still very much unknown about idiopathic autism. Not only differences but also some similarities between Fragile X and IA are discussed in this review. Taking these similarities can help future studies to understand more about the aetiological mechanisms in IA.
It is remarkable that after the studies that have been done researchers still find it difficult to separate the FXS no autism group and the FXS autism group. FXS has many different symptoms and does not always come with autism. Also, there remains a critical need of appropriate animal models and relevant behavioural assays. This can promote the understanding and treatment of the IA and FXS. Taking these suggestions together may help researchers to develop future studies and to create more awareness and certainty about the differences between the disorders. This way people with IA and FXS can be treated the way it is best for them in the future and makes it more easy to come with effective interventions which can contribute and treat intellectual disabled and autistic patients in the future.
There has been a major generalisation when it comes to Fragile X and idiopathic autism. This review shows different sides of the two disorders and the fact that there is not just one factor relevant discussing them. Discussing the genetics, phenotype and behaviour of the two disorders this review is meant to shed a light on both FXS an IA. FXS is caused by a mutation in a single gene; the FMR1 gene. The number and identity of genes involved in IA is largely unknown. Also, epigenetic factors and exposure to environmental modifiers may contribute to variable expression of IA related traits. Phenotypic research showed white matter and grey matter differences between FXS and IA brains. This may be due to the lack of FMRP in FXS brains. FMRP regulates the translation of certain mRNAs that are important for synapse formation and plasticity. Reviewing the behaviour of the two disorders, reciprocal social interaction skills and communication skills are found to be qualitatively less impaired in individuals with FXS than in individuals diagnosed with idiopathic autism. Taking the outcome of the reviewed researches together most studies show a significant difference between the two disorders.
However, it can be determined that there are multiple factors relevant discussing the differences; there are genetic, phenotypic and behavioural differences. Most researches are done examine FXS and idiopathic autism while FXS has many different symptoms and does not always come with autism. It is uncertain whether all the measures are done by participants which are diagnosed with FXS and no autism or not. This may contribute to the outcome in several researches.
By explaining the differences between FXS and IA this review shows an insight in why this generalisation is unseemly. It can be determined that the two disorders are different and that they should be treated differently. Yet, at the present time, there is no accepted therapeutic strategy to treat the core symptoms of idiopathic autism (Zhang et al. 2009). This review can help future investigators to not make the category mistake by classifying both FXS and IA with the same ‘autism’. There is still very much unknown about idiopathic autism. Not only differences but also some similarities between Fragile X and IA are discussed in this review. Taking these similarities can help future studies to understand more about the aetiological mechanisms in IA.
It is remarkable that after the studies that have been done researchers still find it difficult to separate the FXS no autism group and the FXS autism group. FXS has many different symptoms and does not always come with autism. Also, there remains a critical need of appropriate animal models and relevant behavioural assays. This can promote the understanding and treatment of the IA and FXS. Taking these suggestions together may help researchers to develop future studies and to create more awareness and certainty about the differences between the disorders. This way people with IA and FXS can be treated the way it is best for them in the future and makes it more easy to come with effective interventions which can contribute and treat intellectual disabled and autistic patients in the future.
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