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1.
Ann Acad Med Singap ; 53(4): 541-552, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38920181

ABSTRACT

Introduction: Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. Method: A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Results: Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. Conclusion: It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.


Subject(s)
Autism Spectrum Disorder , Humans , Autism Spectrum Disorder/therapy , Singapore , Adolescent , Child , Practice Guidelines as Topic
2.
Ann Acad Med Singap ; 53(3): 142-151, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38920242

ABSTRACT

Introduction: Children from low-income (LI) families often suffer from poor health, with sub-optimal health practices. This cross-sectional study examined the differences in health habits and health-related quality of life (HRQoL) of LI preschool children compared to non-low-income preschool peers (PPG). Method: Using data from the social-health Circle of Care-Health Development Screening Programme (CoC-HDSP) in Singapore, 118 LI children and 304 PPG children aged 18 months to 6 years old and their families were recruited from 13 government-funded preschools. Health practices examined included screen time habits, sleep, nutrition, dental health and the children's HRQoL using PedsQL 4.0 Generic Core Scales. Results: Majority of the children were aged 4-6 years in kindergarten 1 and 2. There were more Malay children in the LI than the PPG (61.9% versus [vs] 29.3%, P<0.001). Low-income children were more likely to have lower-educated parents (P<0.001). The completed vaccination rate in the LI group was lower than those in PPG (84.7% vs 98.0%, P<0.001). More in the LI group utilised emergency services for acute illnesses (P<0.05). Fewer LI children had ever visited a dentist (47.4% vs 75.4%, P<0.001), and more LI children consumed sweetened drinks daily (33.3% vs 8.6%, P<0.001). The LI group reported poorer-quality sleep (48.3% vs 27.2%, P<0.001), though both groups exceeded the daily recommended screen viewing duration. The LI group scored higher in the social (mean 92.4±12.2 vs 84.3±15.3, P<0.001) and emotional (mean 85.2±15.1 vs 76.6±17.3, P<0.001) domains of the PedsQL 4.0 when compared to PPG. Conclusion: Low-income children have poorer health practices, receive less preventive paediatric care, and utilise more emergency services for acute illnesses. These findings are important for developing interventions that work towards improving the health of LI children.


Subject(s)
Poverty , Quality of Life , Humans , Singapore , Cross-Sectional Studies , Child, Preschool , Female , Male , Child , Health Behavior , Oral Health/statistics & numerical data , Infant , Screen Time , Sleep
3.
J Autism Dev Disord ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773032

ABSTRACT

This cross-sectional study aimed to assess Quality of life (QoL) of parents of children on the autism spectrum in Singapore and identify its associated factors. Parents of children (age ≥ 5 years) completed the Quality of Life in Autism scale which measures parental self-rated QoL (higher scores denote greater QoL), and the perceived impact of the child's autism-related behaviors on parents (higher scores denote lesser impact). Information on the child's degree of autism (measured by the Social Responsiveness Scale, second edition [SRS-2]), community and social participation and cognitive and adaptive functioning were also obtained. Participants were 86 parents with mean child age 6.3 years (SD 1.0). Univariate analysis results revealed greater participation in community and social events to be two modifiable factors associated with higher parental QoL. However, these factors were not found to be significant in the multivariate model. Higher autism features (represented by higher parent-rated SRS scores) was associated with a greater perceived impact of the child's behaviors by parents in both univariate and multivariate analyses. Of note, child's cognitive or adaptive skills were not significantly associated with either QoL measure. Equipping parents to handle autism-related behaviors can be useful to reduce their impact on parental QoL. Facilitating community participation for these children may positively influence caregiver QoL as well.

4.
Ann. Acad. Med. Singap ; 53(4): 241-252, 20240429.
Article in English | BIGG - GRADE guidelines | ID: biblio-1560783

ABSTRACT

Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.


Subject(s)
Humans , Child , Adolescent , Patient Care Team , Autism Spectrum Disorder/therapy , Singapore , Delphi Technique , Autism Spectrum Disorder/diagnosis
5.
Focus (Am Psychiatr Publ) ; 22(2): 198-211, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38680976

ABSTRACT

While behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future for ASD. In this article, we provide a review of current psychopharmacological treatment in ASD including those used to address common comorbidities of the condition and upcoming new targeted approaches in autism management. Medications including metformin, arbaclofen, cannabidiol, oxytocin, bumetanide, lovastatin, trofinetide, and dietary supplements including sulforophane and N-acetylcysteine are discussed. Commonly used medications to address the comorbidities associated with ASD including atypical antipsychotics, serotoninergic agents, alpha-2 agonists, and stimulant medications are also reviewed. Targeted treatments in Fragile X syndrome (FXS), the most common genetic disorder leading to ASD, provide a model for new treatments that may be helpful for other forms of ASD. Appeared originally in Neurotherapeutics 2022; 19:248-262.

6.
Article in English | MEDLINE | ID: mdl-38485245

ABSTRACT

This commentary highlights the limitations of many existing population-based studies examining the utility of the Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) in screening for autism. We expound on three major factors: (a) the limited number of screen-negative children who undergo diagnostic evaluations, (b) the substantial number of children who screen positive and were subsequently lost to follow-up (i.e. without further diagnostic evaluations), and (c) the sizeable number of children who did not complete the full two-stage screening process as intended. Each of these factors can lead to erroneous estimates of the psychometric properties, specifically, the sensitivity, specificity, and negative predictive value. Hence, we emphasize the need for future studies to increase the number of children who screen negative and receive a diagnostic evaluation and ensure that these children are selected at random without a higher likelihood for the presence of autism. It is also imperative that concrete steps are taken to minimize the number of screen-positive children who are lost to follow-up both within and after the screening process. Both of these will play a major role in ensuring more robust results from empirical research that can guide the clinical implementation of the M-CHAT-R/F.

7.
Autism ; 28(4): 959-974, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37537880

ABSTRACT

LAY ABSTRACT: Caregivers of autistic children often lack knowledge regarding oral homecare and when and where to see the dentist. To address this need, we developed a series of information on oral health. An autistic child assisted in developing two social stories to showcase a dental visit. A mobile app was developed to deliver the above mentioned. Other features include creation of customised social stories and visual schedule and an inbox to allow dentists to send messages to parents. The developed information and social stories were reviewed by experts and parents. The app also underwent anonymous and independent testing by parents. Overall the information and app were well received by the experts and parents.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Mobile Applications , Child , Humans , Oral Health , Consensus , Caregivers
8.
Front Psychiatry ; 14: 1249071, 2023.
Article in English | MEDLINE | ID: mdl-38034929

ABSTRACT

Background: One of the core features of autism spectrum disorder (ASD) is restricted, repetitive patterns of behavior, interests and activities (RRBs). RRBs are known to adversely affect cognition and adaptive functioning. We explored the relationship of RRBs with cognition and adaptive functioning in children with ASD in an Asian setting. Methods: This cross-sectional study was conducted at a tertiary developmental pediatrics center in Singapore from September 2019 to October 2021. Parent-child dyads (parents and their children ≤7 years old diagnosed with ASD) were recruited. Parents completed the Repetitive Behavior Questionnaire-2 (RBQ-2), which reports total score and two subscales - Motor/Sensory Behaviors (RBQ-2 MS) and Rigidity/Routines/Preoccupation with Restricted Interests (RBQ-2 RRPRI). Standardized assessments included Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS-II). Data analysis utilized descriptive statistics and Pearson's correlation. Results: Parents of 113 children [75.2% male, mean (SD) age 5.0 (1.2) years] participated. Median (IQR) RBQ-2 score was 29.0 (11.0). Significant negative correlations (adjusted for age, gender and family history of ASD) were observed for total RBQ-2 scores with MSEL ELC scores (r = -0.248, n = 101, p = 0.014) and VABS-II ABC scores (r = -0.281, n = 88, p = 0.009). Specifically, these correlations of fair strength were seen only with the RBQ-2 MS subscale for both ELC (r = -0.321, n = 101, p = 0.001) and ABC (r = -0.3478, n = 88, p = 0.001). Conclusion: In children with ASD, severity of RRBs correlated with adverse cognition and adaptive functioning measures in our study, consistent with Western literature. While our study does not show causality, it adds to literature serving as a foundation for further research for both clinicians and researchers to target RRBs in improving outcomes with children in ASD.

9.
Autism ; : 13623613231205748, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37882198

ABSTRACT

LAY ABSTRACT: Systematic screening for autism in early childhood has been suggested to improve eventual outcomes by facilitating earlier diagnosis and access to intervention. However, clinical implementation of screening has to take into account effectiveness and feasibility of use within a healthcare setting for accurate diagnosis of autism. In Singapore, autism screening using a structured screening tool is not currently employed as a part of routine well-child visits for children in primary care clinics. In this study, 5336 children (aged 17-20 months) were screened for autism using the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) during their 18-month well-child visit in seven primary care clinics. Screening and follow-up interviews were administered by nursing staff at each clinic. Children screened positive and a portion of those screened negative then underwent diagnostic assessments to determine whether they met the diagnostic criteria for autism. In total, 113 (2.1%) were screened positive, of which 54 (1.0%) met the criteria for autism. Children who screened positive and received a diagnosis accessed autism-specific intervention at an average age of 22 months. Nurses and physicians rated the acceptability and practicality of the M-CHAT-R/F highly. Therefore, the M-CHAT-R/F questionnaire was an effective and feasible tool for autism screening among 18-month-old children in this study. Future studies will be designed to determine the optimal age of screening and role of repeated screening in Singapore, as well as to better understand any potential improved outcomes nationwide compared with pre-implementation of autism screening.

10.
Int J Dev Neurosci ; 83(8): 715-727, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37724826

ABSTRACT

This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6-40 years, (2) full-scale IQ < 84, and (3) language ≥3-word phrases. ASD symptom severity was determined by Autism Diagnostic Observation Schedule-2 (ADOS-2). Other measures identified non-verbal IQ, adaptive skills, and aberrant behaviors. Molecular measures included blood FMR1 and CYFIP1 mRNA levels, FMRP and MMP9 levels. Analysis of variance (ANOVA) and Spearman's correlations were used to compare ASD severity groups. Data from 54 individuals was included with no/mild (N = 7), moderate (N = 18), and severe (N = 29) ASD. Individuals with high ASD severity had lower adaptive behavior scores (47.48 ± 17.49) than the no/mild group (69.00 ± 20.45, p = 0.0366); they also had more challenging behaviors, lethargy, and stereotypic behaviors. CYFIP1 mRNA expression levels positively correlated with the ADOS-2 comparison score(r2  = 0.33, p = 0.0349), with no significant correlations with other molecular markers. In conclusion, autism symptom severity is associated with more adverse cognitive and adaptive skills and specific behaviors in FXS, whereas CYFIP1 mRNA expression levels may be a potential biomarker for severity of ASD in FXS.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Fragile X Syndrome , Humans , Child , Adolescent , Young Adult , Adult , Fragile X Syndrome/complications , Fragile X Syndrome/genetics , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/psychology , Autistic Disorder/genetics , RNA, Messenger , Cognition , Fragile X Mental Retardation Protein
11.
J Dev Behav Pediatr ; 44(7): e470-e475, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37556593

ABSTRACT

BACKGROUND: Fragile X syndrome (FXS) and fetal alcohol syndrome disorders are both common causes of intellectual disability in children. When both conditions are present in the same individual, the resultant phenotype may make identification of clinical issues and management challenging. CASE PRESENTATION: In this case report, we present a case of triplets who had significant in utero alcohol exposure; 2 of whom also have FXS and the other not having the fragile X mutation. The siblings with FXS have subtle differences in the physical phenotype compared with the other one, who has prominent features of partial fetal alcohol syndrome instead. However, all 3 siblings have intellectual impairment (although this is more severe in the 2 with FXS), meet diagnostic criteria for autism spectrum disorder, and present with severe behavioral challenges. The clinical presentation of the 2 siblings with FXS is much more severe as compared to a child with FXS alone, and this is likely due to the additive effect of in utero alcohol exposure and environmental factors. We discuss the combination of these 2 pathologies and how this can affect the overall clinical presentation. CONCLUSION: In the management of children with FXS, evaluation for other risk factors that can have neurobehavioral sequelae is important, and these can affect clinical presentation and prognosis.


Subject(s)
Autism Spectrum Disorder , Fetal Alcohol Spectrum Disorders , Fragile X Syndrome , Intellectual Disability , Substance-Related Disorders , Child , Female , Pregnancy , Humans , Fragile X Syndrome/complications , Fragile X Syndrome/diagnosis , Autism Spectrum Disorder/etiology , Autism Spectrum Disorder/complications , Fetal Alcohol Spectrum Disorders/diagnosis , Diagnosis, Dual (Psychiatry) , Intellectual Disability/genetics
12.
Cells ; 12(14)2023 07 24.
Article in English | MEDLINE | ID: mdl-37508583

ABSTRACT

This study contributes to a greater understanding of the utility of molecular biomarkers to identify clinical phenotypes of fragile X syndrome (FXS). Correlations of baseline clinical trial data (molecular measures-FMR1 mRNA, CYFIP1 mRNA, MMP9 and FMRP protein expression levels, nonverbal IQ, body mass index and weight, language level, NIH Toolbox, adaptive behavior rating, autism, and other mental health correlates) of 59 participants with FXS ages of 6-32 years are reported. FMR1 mRNA expression levels correlated positively with adaptive functioning levels, expressive language, and specific NIH Toolbox measures. The findings of a positive correlation of MMP-9 levels with obesity, CYFIP1 mRNA with mood and autistic symptoms, and FMR1 mRNA expression level with better cognitive, language, and adaptive functions indicate potential biomarkers for specific FXS phenotypes. These may be potential markers for future clinical trials for targeted treatments of FXS.


Subject(s)
Fragile X Syndrome , Humans , Fragile X Syndrome/diagnosis , Fragile X Syndrome/genetics , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Phenotype , Biomarkers , RNA, Messenger/metabolism
13.
Pediatrics ; 151(6)2023 06 01.
Article in English | MEDLINE | ID: mdl-37203373

ABSTRACT

CONTEXT: The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) is used worldwide to screen for autism spectrum disorder (ASD). OBJECTIVE: To calculate psychometric properties of the M-CHAT-R/F for subsequent diagnosis of ASD. DATA SOURCES: Systematic searches of Medline, Embase, SCOPUS, and Trip Pro databases from January 2014 to November 2021. STUDY SELECTION: Studies were included if they (1) used the M-CHAT-R/F (2) applied standard scoring protocol, (3) used a diagnostic assessment for ASD, and (4) reported at least 1 psychometric property of the M-CHAT-R/F. DATA EXTRACTION: Two independent reviewers completed screening, full-text review, data extraction, and quality assessment, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was used to derive pooled estimates and assess for between-study heterogeneity. RESULTS: Of 667 studies identified, 15 with 18 distinct samples from 10 countries (49 841 children) were used in the meta-analysis. Pooled positive predictive value (PPV), was 57.7% (95% confidence interval [CI] 48.6-66.8, τ2 = 0.031). PPV was higher among high-risk (75.6% [95% CI 66.0-85.2]) than low-risk samples (51.2% [95% CI 43.0-59.5]). Pooled negative predictive value was 72.5% (95% CI 62.5-82.4 τ2 = 0.031), sensitivity was 82.6% (95% CI 76.2-88.9) and specificity 45.7% (95% CI 25.0-66.4). LIMITATIONS: Negative predictive value, sensitivity, and specificity were calculated based on small sample sizes because of limited or no evaluation of screen-negative children. CONCLUSIONS: These results support use of the M-CHAT-R/F as a screening tool for ASD. Caregiver counseling regarding likelihood of an ASD diagnosis after positive screen should acknowledge the moderate PPV.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Humans , Child, Preschool , Autistic Disorder/diagnosis , Autism Spectrum Disorder/diagnosis , Mass Screening/methods , Follow-Up Studies , Checklist/methods
14.
Clin Case Rep ; 11(5): e07345, 2023 May.
Article in English | MEDLINE | ID: mdl-37180323

ABSTRACT

Though early ASD diagnosis is highly stable, this case report describes a rare situation in which symptoms resolved without intervention over a 4 month period. We do not recommend delaying diagnosis in symptomatic children who meet criteria but when major behavioral changes are reported after diagnosis, reevaluation may be beneficial.

15.
Sci Rep ; 13(1): 7050, 2023 04 29.
Article in English | MEDLINE | ID: mdl-37120588

ABSTRACT

Carriers of a premutation allele (PM) in the FMR1 gene are at risk of developing a number of Fragile X premutation asssociated disorders (FXPAC), including Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and Fragile X-associated neuropsychiatric disorders (FXAND). We have recently reported somatic CGG allele expansion in female PM; however, its clinical significance remains unclear. The aim of this study was to examine the potential clinical association between somatic FMR1 allele instability and PM associated disorders. Participants comprised of 424 female PM carriers age 0.3- 90 years. FMR1 molecular measures and clinical information on the presence of medical conditions, were determined for all subjects for primary analysis. Two sub-groups of participants (age ≥ 25, N = 377 and age ≥ 50, N = 134) were used in the analysis related to presence of FXPOI and FXTAS, respectively. Among all participants (N = 424), the degree of instability (expansion) was significantly higher (median 2.5 vs 2.0, P = 0.026) in participants with a diagnosis of attention deficit hyperactivity disorder (ADHD) compared to those without. FMR1 mRNA expression was significantly higher in subjects with any psychiatric disorder diagnosis (P = 0.0017); specifically, in those with ADHD (P = 0.009), and with depression (P = 0.025). Somatic FMR1 expansion was associated with the presence of ADHD in female PM and FMR1 mRNA levels were associated with the presence of mental health disorders. The findings of our research are innovative as they suggest a potential role of the CGG expansion in the clinical phenotype of PM and may potentially guide clinical prognosis and management.


Subject(s)
Fragile X Syndrome , Trinucleotide Repeat Expansion , Female , Humans , Alleles , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , RNA, Messenger , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over
16.
Int J Paediatr Dent ; 33(2): 203-215, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36271894

ABSTRACT

BACKGROUND: Children with autism spectrum disorders (ASD) face challenges in home oral care, accessing a dentist and accepting dental treatment. AIM: To determine the barriers to dental care for autistic children in Singapore through the experiences and opinions of their parents. DESIGN: A qualitative exploratory approach comprising semistructured interviews and a focus group discussion was used. Audio recordings were transcribed and coded into themes using NVivo 12 software. RESULTS: Participants were 23 parents of autistic children aged 3-12 years. The following barriers were identified: (1) Sensory, physical and parental knowledge issues are related to toothbrushing difficulties and use of nonoptimally fluoridated toothpaste in autistic children. (2) Accessing dental services was hindered by a lack of parental knowledge on the importance of an early dental home, parental apprehension about the child's acceptance of dental care, lack of information on specialised dentists and perceived high cost of dental visits. Parental suggestions for improvements included understanding the child's sensory profile, more information on finding a suitable dentist and subsidisation of costs for multiple acclimatisation visits. CONCLUSION: Caregivers' education, information about specialised dentists and the availability of specific dental care resources for autistic children in Singapore are needed for optimising their dental care.


Subject(s)
Autistic Disorder , Dental Care for Children , Humans , Child , Qualitative Research , Adaptation, Psychological , Parents , Dental Care
17.
Genes (Basel) ; 13(12)2022 12 17.
Article in English | MEDLINE | ID: mdl-36553666

ABSTRACT

Background: The fragile X premutation carrier state (PM) (55-200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals.


Subject(s)
Autism Spectrum Disorder , Fragile X Syndrome , Male , Female , Humans , Autism Spectrum Disorder/genetics , Retrospective Studies , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Tremor/genetics
18.
Clin Case Rep ; 10(11): e6586, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36447664

ABSTRACT

Premutation alleles with 55-200 CGG repeats in FMR1 can lead to fragile X-associated tremor/ataxia syndrome (FXTAS). In this case study, we report uncontrolled gout in a 68-year-old male with FXTAS with multiple sites of involvement including a rare gouty tophus in the nasal region.

19.
J Neurol ; 269(9): 4676-4683, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35723724

ABSTRACT

There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD) with multiple forms of ASD having been identified over the decades. Among these, a genetic etiology can be identified in 20-40% of cases when a full genetic work-up is completed. The Fragile X premutation state (characterized by the presence of 55-200 CGG repeats in the FMR1 gene) is a relatively newly identified disease state that has since been associated with several disorders including fragile X-associated tremor ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI) and most recently, fragile X-associated neurodevelopmental disorders (FXAND) which commonly includes anxiety and depression. In addition to these associated disorders, extant literature and clinical observations have suggested an association between the premutation state and ASD. In this paper, we review the literature pertinent to this and discuss possible molecular mechanisms that may explain this association. This includes lowered levels of the FMR1 Protein (FMRP), GABA deficits, mitochondrial dysfunction and secondary genetic abnormalities that is seen in premutation carriers as well as their increased vulnerability to environmental stressors. Understanding these mechanisms can facilitate development of targeted treatment for specific sub-groups of ASD and premutation disorders in future.


Subject(s)
Autism Spectrum Disorder , Fragile X Syndrome , Ataxia/genetics , Autism Spectrum Disorder/genetics , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/complications , Fragile X Syndrome/genetics , Humans , Mutation/genetics
20.
Int J Paediatr Dent ; 32(6): 865-876, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35561086

ABSTRACT

BACKGROUND: Children with autism spectrum disorder (ASD) have challenges in home oral care, accessing a dentist and accepting dental treatment. Occupational therapists (OTs) and speech therapists (STs) are likely to be involved earlier in managing communication, behavioural and sensory processing issues. AIM: To determine perceived issues, barriers and potential solutions to dental care for children with ASD in Singapore from the perspective of OTs and STs. DESIGN: Semi-structured interviews and a focus group discussion involving OTs and STs who treat children with ASD were conducted. Audio recordings were transcribed and coded into themes using the NVivo 12 software. RESULTS: Emergent themes indicated that: (i) OTs and STs have important roles in recognition of issues with toothbrushing, oral pathology and harmful oral habits; (ii) OTs and STs were able to identify reasons for difficulties in oral home care for children with ASD and offer helpful strategies; and (iii) OTs and STs can play a role in pre-dental visit preparations but lack a clear dental referral pathway. CONCLUSIONS: OTs and STs exclusively assist in the early identification and referrals of children with ASD to the dentist. Interprofessional collaboration with dentists should be further explored to aid in the provision of preventive dental advice.


Subject(s)
Autism Spectrum Disorder , Dental Care for Children , Child , Humans , Speech , Toothbrushing
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