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. 2024 Aug 13;19(1):296.
doi: 10.1186/s13023-024-03313-8.

Burden of illness in Rett syndrome: initial evaluation of a disorder-specific caregiver survey

Walter E Kaufmann  1   2 , Alan K Percy  3 , Jeffrey L Neul  4 , Jenny Downs  5 , Helen Leonard  5 , Paige Nues  6 , Girish D Sharma  7 , Theresa E Bartolotta  8 , Gillian S Townend  9 , Leopold M G Curfs  9 , Orietta Mariotti  10 , Claude Buda  11 , Heather M O'Leary  12 , Lindsay M Oberman  13 , Vanessa Vogel-Farley  12 , Katherine V Barnes  12 , Christopher U Missling  12
Affiliations

Burden of illness in Rett syndrome: initial evaluation of a disorder-specific caregiver survey

Walter E Kaufmann et al. Orphanet J Rare Dis. .

Abstract

Background: Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder associated with multiple neurologic impairments. Previous studies have shown challenges to the quality of life of individuals with RTT and their caregivers. However, instruments applied to quantify disease burden have not adequately captured the impact of these impairments on affected individuals and their families. Consequently, an international collaboration of stakeholders aimed at evaluating Burden of Illness (BOI) in RTT was organized.

Methods: Based on literature reviews and qualitative interviews with parents of children and adults with RTT, a caregiver questionnaire was constructed to evaluate 22 problems (inclusive of core characteristics, functional impairments, and comorbidities) often experienced with RTT, rated mainly with a 5-level Likert scale. The questionnaire was administered anonymously online to an international sample of 756 caregivers (predominantly parents) of girls and women with RTT. Descriptive statistics were used to identify problems of high frequency and impact on affected individuals and caregivers. Chi-square tests characterized the relationship between problem severity and impact responses, while nonparametric ANOVAs of raw and z-score adjusted scores identified agreement between severity and impact on individual and caregiver. Secondary inferential tests were used to determine the roles of age, clinical type, and country of residence on BOI in RTT.

Results: There was variability in reported frequency of problems, with the most prevalent, severe and impactful being those related to the core features of RTT (i.e., communication and fine and gross motor impairments). Chi-square analyses demonstrated interdependence between severity and impact responses, while ANOVAs showed that many problems had disproportionately greater impact than severity, either on affected individuals (e.g., hand stereotypies) or their caregivers (e.g., sleep difficulties, seizures, pain, and behavioral abnormalities). With certain exceptions (e.g., breath-holding, seizures), age, clinical type, or country of residence did not influence these BOI profiles.

Conclusions: Our data demonstrate that core features and related impairments are particularly impactful in RTT. However, problems with mild severity can also have disproportionate impact on affected individuals and, particularly, on their caregivers. Future analyses will examine the role of factors such as treatment outcomes, healthcare services, and healthcare provider's perspectives, in these BOI profiles.

Keywords: Caregiver; Intellectual disability; Parent-proxy report; Quality of life; Rett syndrome.

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Conflict of interest statement

WEK is currently the Chief Scientific Officer of Anavex Life Sciences Corp. He received funding from the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), and he has been a consultant for Anavex, AveXis, Acadia, EryDel, Neuren Pharmaceuticals, Newron, GW Pharmaceuticals, Marinus, Biohaven, Zynerba, Ovid Therapeutics, and Stalicla. He has done clinical trials with Neuren. AKP received funding from the NIH and is a consultant for Anavex, Taysha Gene Therapies, Neurogene, and Acadia. He is a member of the DSMB for Taysha Gene Therapies and has done clinical trials with Anavex, Acadia, GW Pharmaceuticals, and the Rett Syndrome Research Trust (RSRT). JLN received funding from the NIH, International Rett Syndrome Foundation (IRSF) and RSRT. He is a consultant for Acadia, Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La Roche, Myrtelle, Neurogene, Newron, Signant Health, Taysha Gene Therapies, and for the preparation of CME activities for PeerView Institute MedEdicus and Medscape; he serves on the scientific advisory board of Alcyone Lifesciences and is a scientific cofounder of LizarBio Therapeutics; and he was also a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. He has done clinical trials with Acadia and Newron. JD has consulted for Marinus, Newron, Orion, Taysha, Neurogene, Acadia and AveXis. She has done clinical trials with Newron and Anavex. HL has consulted for Acadia, Avexis, Anavex, GW Pharmaceuticals, Newron, Neurogene, Marinus, and Ovid Therapeutics. She has received funding from the NIH, International Foundation for CDKL5 Research and the Loulou Foundation. HMO, KVB, ERH, and CUM are Anavex employees. VV-F is a consultant for Anavex. The rest of the authors, PN, GDS, TEB, GST, LMGC, OM, and CB, declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patterns of distribution of responses in caregiver survey: three examples of impact caregiver frequency histograms
See this image and copyright information in PMC

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