Autism Spectrum Disorder
behavior in FXS, (b) examine the stability of autistic ratings over time, and (c) assess the association between the fragile. X mental retardation protein (FMRP) . behavior in FXS, (b) examine the stability of autistic ratings over time, and (c) assess the association between the fragile. X mental retardation protein (FMRP) . BACKGROUND AND OBJECTIVE: Individuals with fragile X syndrome (FXS) are .. Although the association of behavioral problems with FXS+ASD serves to.
Individuals with FXS who also are diagnosed with ASD display social communication impairments and a set of restricted and repetitive behaviors which could be associated with the presence of externalizing behaviors e. These externalizing behaviors in children with FXS may be exacerbated by parental psychopathology which could be independent or associated with child problem behavior Hessl et al. Parents who struggle to cope with the unique demands of their children are likely to have trouble interacting with their children Hessl et al.
While children with FXS typically have a moderate intellectual disability, it is the presence of challenging behaviors that is the primary source of stress and challenge for parents and other caregivers. Examples of autistic behaviors associated with FXS are hand flapping, poor eye contact and tactile defensiveness Tranfaglia, It is highly important to investigate problematic behaviors and their possible indicators because behavioral problems in individuals with FXS can indicate the influence of negative environmental factors Bailey et al.
For example, poor relational functioning within the family as a whole increases the likelihood that the individual with FXS will communicate by means of externalizing behaviors Hessl et al.
These aggressive behaviors may be related to delays in language skills and frustration, consequences due to the inability to communicate Tranfaglia, Individuals with FXS may exhibit aggressive behaviors aligned with their autistic behaviors in that they may be reacting to heightened sensory input or to persons making unrealistic demands on them, which makes them frustrated and potentially aggressive.
Parenting stress refers to how parents cope with the demands of raising a child.
Behavioral relationship between autism and fragile x syndrome.
Raising a child with a developmental disorder includes the time constraints of specialized care, the worry that their child is not reaching their developmental milestones, and the fear that their child will never be fully independent Wolf et al. How parental stress relates to child problem behaviors has been a complex relationship investigators have been invested in understanding. The present study was conducted to examine how fragile X syndrome and aggressive behaviors in male children relate to parenting stress.
However, there is still a lot of debate among researchers and clinicians over prevalence rates of ASD. What does fragile X syndrome have in common with ASD? ASD is typically characterised by difficulties in social behaviour and communication.
In addition, individuals with ASD typically have high levels of repetitive behaviour. Similarly to people with ASD, people with fragile X syndrome tend to show heightened levels of particular repetitive behaviours; for example, stereotyped behaviours and repetitive vocalisations and difficulties in social interaction and communication. While there are similarities between fragile X syndrome and ASD, social behaviours such as social smiling, showing a range of social expressions, quality of social overtures and sharing attention and communicative abilities gesturing, pointing and imitation have been reported to be less impaired in individuals with fragile X syndrome than in individuals with autism spectrum disorder.
Avoiding making eye contact is seen in both fragile X syndrome and ASD but it is likely that this occurs in fragile X syndrome for different reasons than those described in ASD. Screening The discovery of the FMR-1 gene means that, theoretically, DNA-based screening for the premutation could forewarn all potentially affected families. Population-based screening is neither feasible nor ethicalmainly because of the current inability to distinguish full-mutation female fetuses with mental impairment from fetuses whose intelligence is not affected.
Therefore, screening would be targeted at individuals who are at a higher risk. The various proposed strategies include preconceptual testing and routine prenatal screening of all carrier pregnancies. Barriers to implementing even limited paediatric screening and cascade screening in affected families include inadequate resources, difficulties in counselling those with intermediate-range alleles, and the need to achieve uniformly high standards in the existing screening programmes as a prerequisite for any population-based programme.
Management While there is no cure for FXS, many areas of intervention can improve the lives of those affected and their families. All affected people can make progress with proper education, therapy and support. A multidisciplinary approach is necessary to manage the multifaceted problems encountered. Each child should be formally assessed to establish his or her needs. Speech therapists, behavioural therapists, special educators and paediatricians are all likely to be involved.
The early years are of vital importance for stimulating maximum learning in children with the syndrome, and intervention at this stage can prevent many problems later. Services that can be offered include family training to encourage physical, speech and sensory training, and the promotion of a routine for the child, which helps to alleviate anxiety. Genetic counselling If a positive FXS test is discovered, the proband and family should be referred for genetic counselling and cascade testing of family members at risk of carrying a full mutation or permutation McConkie-Rosell et al.
Genetic counselling aims to educate families about the syndrome, its implications and prognosis, supporting them in making informed decisions about the future and in dealing with the emotional impact of the diagnosis. Counselling also identifies others who might need to be alerted about the diagnosis and the availability of testing. Despite the wealth of knowledge regarding the behavioural phenotype of FXS, there are almost no empirical studies on the effectiveness of behavioural treatments among patients with FXS Reiss and Hall, Both animal and human studies have shown that variations in the environment have an impact on behaviour Restivo et al.
A higher-quality home environment is associated with fewer autistic behaviours, better adaptive behaviour, and higher IQ scores in children with FXS Glaser et al.
The authors found that as a result of the programme settling problems, night waking, and co-sleeping were effectively reduced. Psychotherapy and counselling has been applied for higher functioning individuals with FXS Hills-Epstein et al. Psychotherapy or cognitive-behavioural interventions can focus on anxiety reduction through desensitization and other behavioural tools, the discussion and treatment of sexuality issues especially fetishism and other paraphiliasor management of depression Schneider et al.
As autism-like behavioural features are commonly found in the individuals with FXS treatment models used in individuals with autism can be modified and applied to the individuals with FXS. Treatment models that are well established in autism management like Treatment and Education of Autistic and Related Communication-Handicapped Children model Schopler et al.
The authors found that in addition to behavioural intervention and individualized therapies, stimulants were shown to improve symptoms of ADHD in individuals with FXS. Stimulants may not be helpful for children under the age of five as they may cause increased irritability. In both the studies, effects were more remarkable in the parent report rather than teacher report. Antipsychotic medications have been frequently used to address challenging behaviours like aggression and irritability. Risperidone has been the most frequently prescribed antipsychotic medication and has been found to be safe and effective for aggressive individuals with FXS McCracken et al.
Seizures in FXS generally are easily controlled with a single anticonvulsant. Medications like Carbamazipine and Valproate have been used historically to achieve good seizure control. More recently, medications like Lamotrigine, Oxcabazepine, Zonisamide and Levetiracetam have proven to be effective anticonvulsants for patients with seizures that are difficult to control, with the advantage of minimal cognitive adverse effects Hagerman et al.
Side effect profile of the antiepileptic medication should be taken into consideration before prescribing to individuals with FXS.
It has been hypothesised that many psychiatric and neurological symptoms of FXS could be due to unchecked activation of mGluR5. Fenobam, selective mGluR5 antagonist has been found to have anxiolytic properties and have been used safely in the trials in non- FXS populations. New mGluR5 antagonists are being developed and will be tried in the individuals with FXS in the future.
Behavioral relationship between autism and fragile x syndrome. - Semantic Scholar
Lithium has been found to down regulate the mGluR5 system. The study found that lithium can be helpful for stabilising mood in FXS and provides functional benefit. The study results were consistent with the results of previous animal studies. Gamma-amino butyric acid GABA agonists: GABA is the main inhibitory neurotransmitter in brain.
Aarbaclofen inhibits glutamate signalling in the brain and thereby indirectly inhibit excessive mGluR mediated protein synthesis in FXS. Aarbaclofen is currently been studied in clinical trial in individuals with FXS.
Matrix metalloproteinase-9 MMP-9 inhibitor: Minocycline belongs to a group of antibiotics called synthetic tetracyclines. Minocycline inhibits MMP-9 protein. MMPs are involved in normal development and physiological processes such as wound repair and tissue remodelling.Fragile X Syndrome
Excessive MMP-9 activity is believed to contribute to the lax connective tissue phenotype often seen in children with FXS. A recent pilot open-label trial suggest that minocycline has positive effects on behavioural symptoms in individuals with FXS Paribello et al.
Individuals with FXS should also be tested for conductive hearing loss which could result from frequent ear infections. The future There have been significant developments in FXS research in the last two decades.
It is now possible to diagnose FXS early in its course by molecular genetic techniques. Despite in the advances in the genetic testing many individuals with FXS continue to remain undiagnosed. In the future we may see further efforts to implement newborn or infant screening for FXS. While there is no cure for FXS yet, interventions with multidisciplinary approach can improve quality of life of those affected and their families.
There has been growing excitement in the Fragile X research community and among the families of people that have FXS about new developments in the targeted treatments for FXS.
It is hoped that future molecular therapies, whether they are aimed at mGluR5, the AMPA receptor, or other molecular targets, will be directed at preventing the development of some of the symptoms of FXS. In future we may also see Gene therapy interventions developed which may involve placing a functioning copy of the FMR1 gene into the cells of the brain so that the right form of FMRP could be produced in the right place at the right time and in the right amounts.
No change in the age of diagnosis for FXS: The mGluR theory of fragile X mental retardation. Therapeutic implications of the mGluR theory of fragile X mental retardation. Berry-Kravis E, Potanos K.
Open-label treatment trial of lithium to target the underlying defect in FXS.
Fragile-X Syndrome | Intellectual Disability and Health
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