Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire

Hou, Wei; Bhattacharya, Usree; Pradana, Wisnu; Tarquinio, Daniel

doi:10.1016/j.pediatrneurol.2020.01.009

Cited by 26 publications

(20 citation statements)

References 25 publications

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“…The MECP2 mutations R168X and T158M were the most frequent in both studies. The RSBQ results were similar to the score distribution reported by Hou et al (2020). In the future, by obtaining accurate information on gene testing from sources other than the parents, it will be possible to investigate the relationship between genes and the presence of an intervention.…”

Section: Discussionsupporting

confidence: 90%

Comparison of the presence and absence of an intervention to reduce hand stereotypies in individuals with Rett syndrome

Hirano

Goto

Shoji

et al. 2021

Research Intellect Disabil

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Background We investigated how many individuals with Rett syndrome were undergoing interventions to reduce stereotypic hand movements and the factors determining the presence or absence of an intervention. Method A questionnaire was sent to 194 families. Each survey item was compared between the intervention and non‐intervention groups according to the presence or absence of interventions to reduce hand stereotypies. Results Information was acquired from 72 cases; 72.1% of individuals had received an intervention to reduce stereotypies at some point in their lives. An upper limb splint was the most common intervention. Age, locomotor and reaching function, diagnostic age, frequency and type of stereotypy, joint contractures and stereotypy‐associated problems separated the presence or absence of a current or past intervention. Conclusions Interventions for stereotypy‐associated problems are important and there are several variables related to whether an intervention is received.

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Section: Discussionsupporting

confidence: 90%

Comparison of the presence and absence of an intervention to reduce hand stereotypies in individuals with Rett syndrome

Hirano

Goto

Shoji

et al. 2021

Research Intellect Disabil

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“…The search for quantitative biomarkers is instrumental in complex heterogenic rare diseases, like RTT or MDS, especially those biomarkers that could be informative at early stages or used to monitor disease progression and the effect of treatments in clinical trials, as clinical severity scores are not optimal outcome measures [32,47,48]. In particular, the identification of reliable biomarkers for RTT early screening can contribute to a prompt genetic diagnostic, as the main age at RTT diagnosis is 24 months due to the apparently normal development that precedes the onset of overt symptoms [49].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials have mainly focused on RTT patients [31], as the first MDS patients were reported in 2005. To date, only a few trials revealed significant improvements, and one of the reported drawbacks was that clinical severity scores were not optimal outcome measures [32]. Thus, the identification of unbiased quantitative biomarkers that correlate with clinical and/or quality of life data could add great value to the current measures, not only for the follow-up of disease progression in clinical trials but also for aiding early disease diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Unraveling Molecular Pathways Altered in MeCP2-Related Syndromes, in the Search for New Potential Avenues for Therapy

et al. 2021

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Methyl-CpG-binding protein 2 (MeCP2) is an X-linked epigenetic modulator whose dosage is critical for neural development and function. Loss-of-function mutations in MECP2 cause Rett Syndrome (RTT, OMIM #312750) while duplications in the Xq28 locus containing MECP2 and Interleukin-1 receptor-associated kinase 1 (IRAK1) cause MECP2 duplication syndrome (MDS, OMIM #300260). Both are rare neurodevelopmental disorders that share clinical symptoms, including intellectual disability, loss of speech, hand stereotypies, vasomotor deficits and seizures. The main objective of this exploratory study is to identify novel signaling pathways and potential quantitative biomarkers that could aid early diagnosis and/or the monitoring of disease progression in clinical trials. We analyzed by RT-PCR gene expression in whole blood and microRNA (miRNA) expression in plasma, in a cohort of 20 females with Rett syndrome, 2 males with MECP2 duplication syndrome and 28 healthy controls, and correlated RNA expression with disease and clinical parameters. We have identified a set of potential biomarker panels for RTT diagnostic and disease stratification of patients with microcephaly and vasomotor deficits. Our study sets the basis for larger studies leading to the identification of specific miRNA signatures for early RTT detection, stratification, disease progression and segregation from other neurodevelopmental disorders. Nevertheless, these data will require verification and validation in further studies with larger sample size including a whole range of ages.

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“…8 The evaluation of the content validity of the CCSA-Clinician lays a strong foundation to then assess reliability and other aspects of validity. The CCSA-Clinician is ready for formal field testing and stands apart from other severity scales previously developed but not content validated, such as the severity assessments for RTT, 24 -28 FOXG1, 29,30 tuberous sclerosis 31 and other DEEs. 32 Other severity assessments have been content validated with a form that rated items on relevance.…”

Section: Discussionmentioning

confidence: 99%

Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder

et al. 2021

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CDKL5 deficiency disorder (CDD) results in early-onset seizures and severe developmental impairments. A CDD clinical severity assessment (CCSA) was previously developed with clinician and parent-report items to capture information on a range of domains. Consistent with US Food and Drug Administration (FDA) guidelines, content validation is the first step in evaluating the psychometric properties of an outcome measure. The aim of this study was to validate the content of the clinician-reported items in the CCSA (CCSA-Clinician). Eight neurologists leading the USA CDD Center of Excellence clinics were interviewed using the “think aloud” technique to critique 26 clinician-reported items. Common themes were aggregated, and a literature search of related assessments informed item modifications. The clinicians then participated in 2 consensus meetings to review themes and finalize the items. A consensus was achieved for the content of the CCSA-Clinician. Eight of the original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments. This study enabled refinement of the CCSA-Clinician and provided evidence for its content validity. This preliminary validation is essential before field testing and further validation, in order to advance the instrument toward clinical trial readiness.

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Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire

Cited by 26 publications

References 25 publications

Comparison of the presence and absence of an intervention to reduce hand stereotypies in individuals with Rett syndrome

Comparison of the presence and absence of an intervention to reduce hand stereotypies in individuals with Rett syndrome

Unraveling Molecular Pathways Altered in MeCP2-Related Syndromes, in the Search for New Potential Avenues for Therapy

Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder

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