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Journal of Autism and Developmental Disorders

Gepubliceerd in:

05-03-2024 | Original Article

Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS)

Auteurs: Melissa Raspa, Angela Gwaltney, Carla Bann, Jana von Hehn, Timothy A. Benke, Eric D. Marsh, Sarika U. Peters, Amitha Ananth, Alan K. Percy, Jeffrey L. Neul

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 3/2025

Abstract

Rett syndrome is a severe neurodevelopmental disorder that affects about 1 in 10,000 females. Clinical trials of disease modifying therapies are on the rise, but there are few psychometrically sound caregiver-reported outcome measures available to assess treatment benefit. We report on a new caregiver-reported outcome measure, the Rett Caregiver Assessment of Symptom Severity (RCASS). Using data from the Rett Natural History Study (n = 649), we examined the factor structure, using both exploratory and confirmatory factor analysis, and the reliability and validity of the RCASS. The four-factor model had the best overall fit, which covered movement, communication, behavior, and Rett-specific symptoms. The RCASS had moderate internal consistency. Strong face validity was found with age and mutation type, and convergent validity was established with other similar measures, including the Revised Motor-Behavior Assessment Scale, Clinical Severity Scale, Clinical Global Impression Scale, and the Child Health Questionnaire. These data provide initial evidence that the RCASS is a viable caregiver-outcome measure for use in clinical trials in Rett syndrome. Future work to assess sensitivity to change and other measures of reliability, such as test–retest and inter-rater agreement, are needed.

vorige artikel A Measurement Invariance Analysis of the Anxiety Scale for Autism–Adults in a Sample of Autistic and Non-Autistic Men and Women

volgende artikel A Systematic Literature Review of Racial Disproportionality in Autism in the U.S.

Alleen toegankelijk voor geautoriseerde gebruikers

Aman, M. G., & Singh, N. B. (1994). Aberrant behavior checklist—Community. Slosson Educational Publications.

Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23(2), 185–188. https://doi.org/10.1038/13810CrossRefPubMed

Amir, R. E., & Zoghbi, H. Y. (2000). Rett syndrome: Methyl-CpG-binding protein 2 mutations and phenotype–genotype correlations. American Journal of Medical Genetics, 97(2), 147–152. https://doi.org/10.1002/1096-8628(200022)97:2%3C147::aid-ajmg6%3E3.0.co;2-oCrossRefPubMed

Barnes, K. V., Coughlin, F. R., O’Leary, H. M., Bruck, N., Bazin, G. A., Beinecke, E. B., & Kaufmann, W. E. (2015). Anxiety-like behavior in Rett syndrome: Characteristics and assessment by anxiety scales. Journal of Neurodevelopmental Disorders, 7(1), 1–14. https://doi.org/10.1186/s11689-015-9127-4CrossRef

Benjamin, K., Vernon, M. K., Patrick, D. L., Perfetto, E., Nestler-Parr, S., & Burke, L. (2017). Patient-reported outcome and observer-reported outcome assessment in rare disease clinical trials: An ISPOR COA emerging good practices task force report. Value in Health, 20(7), 838–855. https://doi.org/10.1016/j.jval.2017.05.015CrossRefPubMed

Berry-Kravis, E., Hessl, D., Abbeduto, L., Reiss, A. L., Beckel-Mitchener, A., Urv, T. K., Group, O. M. W. (2013). Outcome measures for clinical trials in fragile X syndrome. Journal of Developmental and Behavioral Pediatrics, 34(7), 508. https://doi.org/10.1097/dbp.0b013e31829d1f20CrossRefPubMedPubMedCentral

Buchanan, C. B., Stallworth, J. L., Scott, A. E., Glaze, D. G., Lane, J. B., Skinner, S. A., & Kaufmann, W. E. (2019). Behavioral profiles in Rett syndrome: Data from the natural history study. Brain and Development, 41(2), 123–134. https://doi.org/10.1016/j.braindev.2018.08.008CrossRefPubMed

Bushby, K., & Connor, E. (2011). Clinical outcome measures for trials in Duchenne muscular dystrophy: Report from International Working Group meetings. Clinical Investigation, 1(9), 1217. https://doi.org/10.4155/cli.11.113CrossRefPubMedPubMedCentral

Corchón, S., Carrillo-López, I., & Cauli, O. (2018). Quality of life related to clinical features in patients with Rett syndrome and their parents: A systematic review. Metabolic Brain Disease, 33(6), 1801–1810. https://doi.org/10.1007/s11011-018-0316-1CrossRefPubMed

Cuddapah, V. A., Pillai, R. B., Shekar, K. V., Lane, J. B., Motil, K. J., Skinner, S. A., & Olsen, M. L. (2014). Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. Journal of Medical Genetics, 51(3), 152–158. https://doi.org/10.1530/boneabs.7.p118CrossRefPubMed

Esbensen, A. J., Hooper, S. R., Fidler, D., Hartley, S. L., Edgin, J., d’Ardhuy, X. L., Group, O. M. W. (2017). Outcome measures for clinical trials in Down syndrome. American Journal on Intellectual and Developmental Disabilities, 122(3), 247–281. https://doi.org/10.1352/1944-7558-122.3.247CrossRefPubMedPubMedCentral

Esbensen, A. J., Rojahn, J., Aman, M. G., & Ruedrich, S. (2003). Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. Journal of Autism and Developmental Disorders, 33, 617–629. https://doi.org/10.1023/b:jadd.0000005999.27178.55CrossRefPubMed

Farmer, C., Kaat, A. J., Berry-Kravis, E., & Thurm, A. (2022). Psychometric perspectives on developmental outcome and endpoint selection in treatment trials for genetic conditions associated with neurodevelopmental disorder. In International review of research in developmental disabilities (Vol. 62, pp. 1–39). Academic Press.

Fischer, J. S., Rudick, R. A., Cutter, G. R., Reingold, S. C., National MS Society Clinical Outcomes Assessment Task Force. (1999). The multiple sclerosis functional composite measure (MSFC): An integrated approach to MS clinical outcome assessment. Multiple Sclerosis Journal, 5(4), 244–250. https://doi.org/10.1177/135245859900500409CrossRefPubMed

Food and Drug Administration (March, 2023). FDA approves first treatment for Rett Syndrome. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-rett-syndrome#:~:text=FDA%20has%20approved%20Daybue%20(trofinetide,orally%20or%20via%20gastrostomy%20tube. Accessed November 30, 2023.

Fu, C., Armstrong, D., Marsh, E., Lieberman, D., Motil, K., Witt, R., & Benke, T. (2020). Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. https://doi.org/10.1136/bmjpo-2020-000717CrossRefPubMedPubMedCentral

Glaze, D. G., Neul, J. L., Kaufmann, W. E., Berry-Kravis, E., Condon, S., Stoms, G., & Percy, A. K. (2019). Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology, 92(16), e1912–e1925. https://doi.org/10.1212/wnl.0000000000007316CrossRefPubMedPubMedCentral

Glaze, D. G., Neul, J. L., Percy, A., Feyma, T., Beisang, A., Yaroshinsky, A., & Jones, N. E. (2017). A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of Rett syndrome. Pediatric Neurology, 76, 37–46. https://doi.org/10.1016/j.pediatrneurol.2017.07.002CrossRefPubMed

Guy, J., Gan, J., Selfridge, J., Cobb, S., & Bird, A. (2007). Reversal of neurological defects in a mouse model of Rett syndrome. Science, 315(5815), 1143–1147. https://doi.org/10.3410/f.1066718.519633CrossRefPubMedPubMedCentral

Hagberg, B., Aicardi, J., Dias, K., & Ramos, O. (1983). A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: Report of 35 cases. Annals of Neurology, 14(4), 471–479. https://doi.org/10.1002/ana.410140412CrossRefPubMed

Hou, W., Bhattacharya, U., Pradana, W. A., & Tarquinio, D. C. (2020). Assessment of a clinical trial metric for Rett syndrome: Critical analysis of the Rett syndrome behavioural questionnaire. Pediatric Neurology, 107, 48–56. https://doi.org/10.1016/j.pediatrneurol.2020.01.009CrossRefPubMed

Hurley, E. N., Ellaway, C. J., Johnson, A. M., Truong, L., Gordon, R., Galettis, P., & Lawson, J. A. (2022). Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial. Epilepsia, 63(7), 1736–1747. https://doi.org/10.1111/epi.17247CrossRefPubMedPubMedCentral

Katz, D. M., Bird, A., Coenraads, M., Gray, S. J., Menon, D. U., Philpot, B. D., & Tarquinio, D. C. (2016). Rett syndrome: Crossing the threshold to clinical translation. Trends in Neurosciences, 39(2), 100–113. https://doi.org/10.1016/j.tins.2015.12.008CrossRefPubMedPubMedCentral

Killian, J. T., Jr., Lane, J. B., Lee, H. S., Pelham, J. H., Skinner, S. A., Kaufmann, W. E., & Percy, A. K. (2016). Caretaker quality of life in Rett syndrome: Disorder features and psychological predictors. Pediatric Neurology, 58, 67–74. https://doi.org/10.1016/j.pediatrneurol.2015.12.021CrossRefPubMedPubMedCentral

Landgraf, J. M., Abetz, L., & Ware, J. E. (1996). The CHQ user’s manual (1st ed.). The Health Institute, New England Medical Center.

Lane, J. B., Lee, H. S., Smith, L. W., Cheng, P., Percy, A. K., Glaze, D. G., & Krischer, J. P. (2011). Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology, 77(20), 1812–1818. https://doi.org/10.1212/wnl.0b013e3182377dd2CrossRefPubMedPubMedCentral

Leonard, H., Bower, C., & English, D. (1997). The prevalence and incidence of Rett syndrome in Australia. European Child & Adolescent Psychiatry, 6(Suppl 1), 8–10. PMID: 9452912.

Leonard, H., Gold, W., Samaco, R., Sahin, M., Benke, T., & Downs, J. (2022). Improving clinical trial readiness to accelerate development of new therapeutics for Rett syndrome. Orphanet Journal of Rare Diseases, 17(1), 1–15. https://doi.org/10.1186/s13023-022-02240-wCrossRef

Mount, R. H., Charman, T., Hastings, R. P., Reilly, S., & Cass, H. (2002). The Rett syndrome behaviour questionnaire (RSBQ): Refining the behavioural phenotype of Rett syndrome. Journal of Child Psychology and Psychiatry, 43(8), 1099–1110. https://doi.org/10.1111/1469-7610.00236CrossRefPubMed

Muthén, L. K. and Muthén, B. O. (1998–2017). Mplus user’s guide (8th ed.). Muthén & Muthén

National Library of Medicine (2023a). Safety and Efficacy of TSHA-102 in Adult Females With Rett Syndrome (REVEAL Adult Study). https://clinicaltrials.gov/study/NCT05606614. Accessed November 29, 2023.

National Library of Medicine (2023b). A Novel, Regulated Gene Therapy (NGN-401) Study for Female Children With Rett Syndrome. https://clinicaltrials.gov/study/NCT05898620. Accessed November 29, 2023.

Neul, J. L., Benke, T. A., Marsh, E. D., Suter, B., Silveira, L., Fu, C., … & Percy, A. K. (2023). Top caregiver concerns in Rett syndrome and related disorders; Data from the U. S. Natural History Study. Preprint: https://www.researchsquare.com/article/rs-2566253/v1

Neul, J. L., Benke, T. A., Marsh, E. D., Skinner, S. A., Merritt, J., Lieberman, D. N., & Percy, A. K. (2019). The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 180(1), 55–67. https://doi.org/10.1002/ajmg.b.32707CrossRef

Neul, J. L., Fang, P., Barrish, J., Lane, J., Caeg, E. B., Smith, E. O., & Glaze, D. G. (2008). Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology, 70(16), 1313–1321. https://doi.org/10.1212/01.wnl.0000291011.54508.aaCrossRefPubMed

Neul, J. L., Glaze, D. G., Percy, A. K., Feyma, T., Beisang, A., Dinh, T., & Jones, N. E. (2015). Improving treatment trial outcomes for Rett syndrome: The development of Rett-specific anchors for the clinical global impression scale. Journal of Child Neurology, 30(13), 1743–1748. https://doi.org/10.1177/0883073815579707CrossRefPubMedPubMedCentral

Neul, J. L., Kaufmann, W. E., Glaze, D. G., Christodoulou, J., Clarke, A. J., Bahi-Buisson, N., RettSearch Consortium (Members listed in the Appendix). (2010). Rett syndrome: Revised diagnostic criteria and nomenclature. Annals of Neurology, 68(6), 944–950. https://doi.org/10.1002/ana.22124CrossRefPubMedPubMedCentral

Neul, J. L., Lane, J. B., Lee, H. S., Geerts, S., Barrish, J. O., Annese, F., & Percy, A. K. (2014). Developmental delay in Rett syndrome: Data from the natural history study. Journal of Neurodevelopmental Disorders, 6(1), 1–9. https://doi.org/10.1186/1866-1955-6-20CrossRef

Neul, J. L., Percy, A. K., Benke, T. A., Berry-Kravis, E. M., Glaze, D. G., Marsh, E. D., & Youakim, J. M. (2023). Trofinetide for the treatment of Rett syndrome: A randomized Phase 3 study. Nature Medicine. https://doi.org/10.1038/s41591-023-02398-1CrossRefPubMedPubMedCentral

Neul, J. L., Percy, A. K., Benke, T. A., Berry-Kravis, E. M., Glaze, D. G., Peters, S. U., & Youakim, J. M. (2022). Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemporary Clinical Trials, 114, 106704. https://doi.org/10.1016/j.cct.2022.106704CrossRefPubMed

Panayotis, N., Ehinger, Y., Felix, M. S., & Roux, J. C. (2023). State-of-the-art therapies for Rett syndrome. Developmental Medicine & Child Neurology, 65(2), 162–170. https://doi.org/10.1111/dmcn.15383CrossRef

Pozzo-Miller, L., Pati, S., & Percy, A. K. (2015). Rett syndrome: Reaching for clinical trials. Neurotherapeutics, 12(3), 631–640. https://doi.org/10.1007/s13311-015-0353-yCrossRefPubMedPubMedCentral

Raspa, M., Bann, C. M., Gwaltney, A., Benke, T. A., Fu, C., Glaze, D. G., & Neul, J. L. (2020). A psychometric evaluation of the motor-behavioral assessment scale for use as an outcome measure in Rett syndrome clinical trials. American Journal on Intellectual and Developmental Disabilities, 125(6), 493–509. https://doi.org/10.1352/1944-7558-125.6.493CrossRefPubMedPubMedCentral

Ricceri, L., De Filippis, B., & Laviola, G. (2008). Mouse models of Rett syndrome: From behavioural phenotyping to preclinical evaluation of new therapeutic approaches. Behavioural Pharmacology, 19(5–6), 501–517. https://doi.org/10.1097/fbp.0b013e32830c3645CrossRefPubMed

Robinson, L., Guy, J., McKay, L., Brockett, E., Spike, R. C., Selfridge, J., & Cobb, S. R. (2012). Morphological and functional reversal of phenotypes in a mouse model of Rett syndrome. Brain, 135(9), 2699–2710. https://doi.org/10.1093/brain/aws096CrossRefPubMedPubMedCentral

Ross, C. A., Aylward, E. H., Wild, E. J., Langbehn, D. R., Long, J. D., Warner, J. H., & Tabrizi, S. J. (2014). Huntington disease: Natural history, biomarkers and prospects for therapeutics. Nature Reviews Neurology, 10(4), 204–216. https://doi.org/10.1038/nrneurol.2014.24CrossRefPubMed

Schreiber, J. B., Nora, A., Stage, F. K., Barlow, E. A., & King, J. (2006). Reporting structural equation modeling and confirmatory factor analysis results: A review. The Journal of Educational Research, 99(6), 323–338. https://doi.org/10.3200/joer.99.6.323-338CrossRef

Singh, J., Fiori, F., Law, M. L., Ahmed, R., Ameenpur, S., Basheer, S., & Santosh, P. (2022). Development and psychometric properties of the multi-system profile of symptoms scale in patients with Rett syndrome. Journal of Clinical Medicine, 11(17), 5094. https://doi.org/10.3390/jcm11175094CrossRefPubMedPubMedCentral

Tavakol, M., & Dennick, R. (2011). Making sense of Cronbach’s alpha. International Journal of Medical Education, 2, 53–55. https://doi.org/10.5116/ijme.4dfb.8dfdCrossRefPubMedPubMedCentral

Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., & Sur, M. (2009). Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proceedings of the National Academy of Sciences, 106(6), 2029–2034. https://doi.org/10.1073/pnas.0812394106CrossRef

Whittal, A., Meregaglia, M., & Nicod, E. (2021). The use of patient-reported outcome measures in rare diseases and implications for health technology assessment. The Patient – Patient-Centered Outcomes Research, 14(5), 485–503. https://doi.org/10.1007/s40271-020-00493-wCrossRefPubMed

Titel: Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS)
Auteurs: Melissa Raspa
Angela Gwaltney
Carla Bann
Jana von Hehn
Timothy A. Benke
Eric D. Marsh
Sarika U. Peters
Amitha Ananth
Alan K. Percy
Jeffrey L. Neul
Publicatiedatum: 05-03-2024
Uitgeverij: Springer US
Gepubliceerd in: Journal of Autism and Developmental Disorders / Uitgave 3/2025
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI: https://doi.org/10.1007/s10803-024-06238-0

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Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS)

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