The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary

Riley, Catharine; Mailick, Marsha R.; Berry‐Kravis, Elizabeth; Bolen, Julie

doi:10.1542/peds.2016-1159b

Cited by 15 publications

(10 citation statements)

References 47 publications

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“…FXS is caused by an unstable expansion of CGG (>200 repeats) in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene leading to reduced or lack of expression of the corresponding fragile X mental retardation protein (FMRP). The absence or deficiency of FMRP disrupts overall translational control generating the overproduction of dendritic protein which causes the abnormal synaptic plasticity characteristic of FXS [Riley, Mailick, Berry‐Kravis, & Bolen, ]. Most of the affected individuals present an autistic‐like clinical profile, characterized by cognitive and behavioral disorders [Diallo et al, ].…”

Section: Introductionmentioning

confidence: 99%

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

et al. 2019

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Autism spectrum disorder (ASD) has been associated with low cholesterol levels in a limited number of studies. However, the prevalence of hypocholesterolemia as well as the degree of association with ASD remains to be elucidated. We therefore sought to investigate the lipid profiles of a group of French‐Canadian ASD individuals. The medical records of 79 ASD individuals and 79 age and gender‐matched healthy controls were retrospectively reviewed. The fasting lipid profiles including total cholesterol (TC), high‐density lipoprotein, triglycerides, and low‐density lipoprotein were extracted for individuals of both groups along with the following clinical data: anthropometric measurements, medication use and associated disorders. Lipid parameters were compared to age and gender‐based normative population and categorized in centile groups. The prevalence of hypocholesterolemia was revealed to be more than threefold higher in ASD individuals as compared to the general population (23%; P = 0.005). The 25th centile was determined as a potential TC threshold that could best predict the ASD (odds ratio [OR] = 3.04; 95% confidence interval [CI]: 1.58–6.65; P < 0.001). This study identified specific ASD comorbidities associated with hypocholesterolemia: TC levels below the 10th centile were associated with a higher rate of ASD‐associated intellectual disability (OR = 3.33; 95% CI: 1.26–8.00) and anxiety/depression (OR = 4.74; 95% CI: 1.40–15.73). Overall, these results support a potential association between hypocholesterolemia and ASD occurrence. Application of this study to larger populations is urging to provide more extensive data that may further elucidate the association between hypocholesterolemia and ASD. Autism Res 2019, 12: 1860–1869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Association of autism spectrum disorder (ASD) with abnormally low levels of cholesterol (hypocholesterolemia) has been documented before. These studies were incomplete, and the conclusion remains speculative. Here, we reviewed the medical records of 79 French‐Canadian ASD individuals and compared their total cholesterol (TC) levels to healthy individuals matched for age and gender. We observed four times more hypocholesterolemia in ASD than in the general population. Furthermore, low TC in ASD was associated with higher rates of ASD‐associated intellectual disability and anxiety/depression. Our results support an association between hypocholesterolemia and ASD and open novel opportunities for the diagnosis and treatment of specific forms of ASD.

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Section: Introductionmentioning

confidence: 99%

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

et al. 2019

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“…As discussed at the 2014 Centers for Disease Control and Prevention FXS stakeholder meeting, the ability to address these issues cannot fall to 1 agency or organization. 30 Addressing barriers and developing evidence will take a community of clinicians, researchers, public health professionals, educational specialists, behavioral specialists, advocates for the FXS population, and individuals with FXS and their families all coming together to move future research activities forward.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Fragile X Syndrome Newborn Screening Landscape

Riley

Wheeler

2017

Pediatrics

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Background Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. Methods A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. Results The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. Conclusions The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life.

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“…Fragile X syndrome is the most common inherited mental impairment and also the most common known single genetic cause of ASD, with a total frequency of approximately 1 in 4,000 males and 1 in 8,000 females ( Riley et al, 2017 ). Individuals with FXS exhibit a broad range of symptoms, including intellectual disabilities, autism, macroorchidism, seizures, sensory hypersensitivity, and facial abnormalities such as a long face and large ears ( Garber et al, 2008 ).…”

Section: In Vivo Optical Imaging Of Fxs Model Micementioning

confidence: 99%

Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models

et al. 2018

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In vivo optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from in vivo imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fragile X syndrome, Rett syndrome, and Angelman syndrome, which are caused by genetic abnormalities of FMR1, MECP2, and UBE3A, as well as disorders caused by copy number variations (15q11-13 duplication and 22q11.2 deletion) and BTBR mice as an inbred strain model of autism spectrum disorder (ASD). Most studies visualize the structural and functional responsiveness of cerebral cortical neurons to sensory stimuli and the developmental and experience-dependent changes in these responses as a model of brain functions affected by these disorders. The optical imaging techniques include two-photon microscopy of fluorescently labeled dendritic spines or neurons loaded with fluorescent calcium indicators and macroscopic imaging of cortical activity using calcium indicators, voltage-sensitive dyes or intrinsic optical signals. Studies have revealed alterations in the density, stability, and turnover of dendritic spines, aberrant cortical sensory responses, impaired inhibitory function, and concomitant failure of circuit maturation as common causes for neurological deficits. Mechanistic hypotheses derived from in vivo imaging also provide new directions for therapeutic interventions. For instance, it was recently demonstrated that early postnatal administration of a selective serotonin reuptake inhibitor (SSRI) restores impaired cortical inhibitory function and ameliorates the aberrant social behaviors in a mouse model of ASD. We discuss the potential use of SSRIs for treating ASDs in light of these findings.

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The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary

Cited by 15 publications

References 47 publications

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

Assessing the Fragile X Syndrome Newborn Screening Landscape

Common Defects of Spine Dynamics and Circuit Function in Neurodevelopmental Disorders: A Systematic Review of Findings From in Vivo Optical Imaging of Mouse Models

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