Advertisement

Wiener Medizinische Wochenschrift

, Volume 166, Issue 11–12, pp 338–345 | Cite as

Quantitative and qualitative insights into the experiences of children with Rett syndrome and their families

  • Jenny Downs
  • Helen Leonard
main topic

Summary

Rett syndrome is a rare neurodevelopmental disorder caused by a mutation in the MECP2 gene. It is associated with severe functional impairments and medical comorbidities such as scoliosis and poor growth. The population-based and longitudinal Australian Rett Syndrome Database was established in 1993 and has supported investigations of the natural history of Rett syndrome and effectiveness of treatments, as well as a suite of qualitative studies to identify deeper meanings. This paper describes the early presentation of Rett syndrome, including regression and challenges for families seeking a diagnosis. We discuss the importance of implementing strategies to enhance daily communication and movement, describe difficulties interpreting the presence of pain and discomfort, and argue for a stronger evidence base in relation to management. Finally, we outline a framework for understanding quality of life in Rett syndrome and suggest areas of life to which we can direct efforts in order to improve quality of life. Each of these descriptions is illustrated with vignettes of child and family experiences. Clinicians and researchers must continue to build this framework of knowledge and understanding with efforts committed to providing more effective treatments and supporting the best quality of life for those affected.

Keywords

Rett syndrome Qualitative research Developmental disability Comorbidity Quality of life 

Quantitative und qualitative Einblicke in die Erfahrungen von Kindern mit Rett-Syndrom und ihren Familien

Zusammenfassung

Das Rett-Syndrom ist eine seltene neurologische Entwicklungsstörung, die durch eine Mutation im MECP2-Gen verursacht wird. Es geht mit schweren funktionellen Beeinträchtigungen und Komorbiditäten wie Skoliose und Wachstumsstörungen einher. Die populationsbasierte und longitudinal ausgerichtete australische Rett-Syndrom-Datenbank (Australian Rett Syndrome Database) wurde 1993 eingerichtet und dient seitdem Untersuchungen des natürlichen Verlaufs des Rett-Syndroms und der Wirksamkeit von Therapien sowie einer Reihe qualitativer Studien zur Erkennung tieferer Zusammenhänge. In der vorliegenden Arbeit werden die Frühsymptome des Rett-Syndroms einschließlich der Regression und der Herausforderungen für die Familien auf der Suche nach einer Diagnose beschrieben. Es werden die Bedeutung der Etablierung von Strategien zur verstärkten alltäglichen Kommunikation und Bewegung erörtert, die Schwierigkeiten bei der Interpretation vorhandener Schmerzen und Unwohlsein genannt und Argumente für eine stärkere Evidenzbasis hinsichtlich der Versorgung angeführt. Schließlich werden ein Bezugsrahmen zum Verständnis der Lebensqualität bei Rett-Syndrom skizziert und Lebensbereiche vorgeschlagen, auf die sich Bemühungen zur Verbesserung der Lebensqualität richten können. Jede dieser Beschreibungen wird mit Falldarstellungen der Erfahrungen eines Kindes und seiner Familie illustriert. Aufgabe der Kliniker und Wissenschaftler ist die kontinuierliche Arbeit an diesem Bezugsrahmen zum Fachwissen und Verständnis in dem Bemühen, wirksamere Behandlungen verfügbar zu machen und die bestmögliche Lebensqualität für die Betroffenen aufrechtzuerhalten.

Schlüsselwörter

Rett-Syndrom Qualitative Untersuchung Entwicklungsbedingte Behinderung Komorbidität Lebensqualität 

Notes

Acknowledgements

We express our special appreciation to all the families and carers of females with Rett syndrome who have contributed to the Australian Rett Syndrome Database. We thank the Australian Paediatric Surveillance Unit (APSU) for collaboration in case ascertainment, and the paediatricians and health professionals who were specifically involved. We also thank Bill Callaghan and the Rett Syndrome Association of Australia for their important contribution to case ascertainment over the years. The Australian Rett syndrome research program has previously been funded by the National Institutes of Health (5R01HD043100-05) and the National Health and Medical Research Council (NHMRC) project grants #303189 and #1004384, and an NHMRC program grant #572742. The projects developing guidelines for gastrointestinal and bone health received funding from RettUK. Dr Helen Leonard’s funding (2009–2014) was previously from an NHMRC Senior Research Fellowship, #572568. The funding bodies for this study have not been involved in study design, data collection, data analysis, manuscript preparation and/or publication decisions. Finally, we thank the many team members and students who have worked with the ARSD and we particularly thank Ms. Amy Epstein, Ms. Anna Urbanowicz, Ms. Janice Lim, Ms. Joanne Lee, Ms. Caitlin Marr and Mr. Thomas Horne for their careful attention to qualitative methodologies.

Conflict of interest

The author(s) declare that they have no competing interests.

References

  1. 1.
    Fehr S, Bebbington A, Nassar N, Downs J, Ronen GM, De Klerk N, et al. Trends in the diagnosis of Rett syndrome in Australia. Pediatr Res. 2011;70(3):313–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X‑linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Samaco RC, Neul JL. Complexities of Rett syndrome and MeCP2. J Neurosci. 2011;31(22):7951–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, et al. Rett syndrome: Revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68:944–50.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bao X, Downs J, Wong K, Williams S, Leonard H. Using a large international sample to investigate epilepsy in Rett syndrome. Dev Med Child Neurol. 2013;55(6):553–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Downs J, Torode I, Wong K, Ellaway C, Elliott EJ, Christodoulou J, et al. The natural history of scoliosis in females with Rett syndrome. Spine. 2016;41(10):856–63.CrossRefPubMedGoogle Scholar
  7. 7.
    Whittingham K, Wee D, Sanders MR, Boyd R. Predictors of psychological adjustment, experienced parenting burden and chronic sorrow symptoms in parents of children with cerebral palsy. Child Care Health Dev. 2013;39(3):366–73.CrossRefPubMedGoogle Scholar
  8. 8.
    Leonard H. Rett syndrome in Australlia. : The University of Western Australia; 1995.Google Scholar
  9. 9.
    Downs J, Leonard H. Longitudinal and population-based approaches to the study of the lifelong trajectories of children with neurodevelopmental conditions. In: Ronen GM, Rosenbaum PL, editors. Life quality outcomes in children and young people with neurological and developmental conditions. London: Mac Keith Press; 2013. pp. 329–43.Google Scholar
  10. 10.
    Downs J, Torode I, Wong K, Ellaway C, Elliott EJ, Izatt MT, et al. Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: A cohort study. Dev Med Child Neurol. 2016;58:632–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Leonard H, Bower C. Is the girl with Rett syndrome normal at birth? Dev Med Child Neurol. 1998;40(2):115–21.PubMedGoogle Scholar
  12. 12.
    Einspieler C, Kerr AM, Prechtl HF. Is the early development of girls with Rett disorder really normal? Pediatr Res. 2005;57(5 Pt 1):696–700.CrossRefPubMedGoogle Scholar
  13. 13.
    Marschik PB, Kaufmann WE, Sigafoos J, Wolin T, Zhang D, Bartl-Pokorny KD, et al. Changing the perspective on early development of Rett syndrome. Res Dev Disabil. 2013;34(4):1236–9.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Segawa M. Early motor disturbances in Rett syndrome and its pathophysiological importance. Brain Dev. 2005;27(Suppl 1):S54–S58.CrossRefPubMedGoogle Scholar
  15. 15.
    Fehr S, Downs J, Bebbington A, Leonard H. Atypical presentations and specific genotypes are associated with a delay in diagnosis in diagnosis in females with Rett syndrome. Am J Med Genet A. 2010;152A:2535–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Bebbington A, Anderson A, Ravine D, Fyfe S, Pineda M, de Klerk N, et al. Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology. 2008;70(11):868–75.CrossRefPubMedGoogle Scholar
  17. 17.
    Downs J, Stahlhut M, Wong K, Syhler B, Bisgaard AM, Jacoby P, et al. Validating the Rett Syndrome Gross Motor Scale. PLoS ONE. 2016;11(1):e0147555.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, et al. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc Natl Acad Sci USA. 2015;112(17):5509–14.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Carter P, Downs J, Bebbington A, Williams S, Jacoby P, Kaufmann WE, et al. Stereotypical hand movements in 144 subjects with Rett syndrome from the population-based Australian database. Mov Disord. 2010;25(3):282–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Lee J, Leonard H, Piek J, Downs J. Early development and regression in Rett syndrome. Clin Genet. 2013; doi: 10.1111/cge.12110.PubMedCentralGoogle Scholar
  21. 21.
    Lim F, Downs J, Li J, Bao XH, Leonard H. Barriers to diagnosis of a rare neurological disorder in China – lived experiences of Rett syndrome families. Am J Med Genet A. 2012;158a(1):1–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Knott M, Leonard H, Downs J. The diagnostic odyssey to Rett syndrome: The experience of an Australian family. Am J Med Genet A. 2012;158A(1):10–2.CrossRefPubMedGoogle Scholar
  23. 23.
    World Health Organization. International Classification of Functioning, Disability and Health: ICF. Geneva: World Health Organisation; 2001.Google Scholar
  24. 24.
    Leonard H, Fyfe S, Leonard S, Msall M. Functional status, medical impairments, and rehabilitation resources in 84 females with Rett syndrome: A snapshot across the world from the parental perspective. Disabil Rehabil. 2001;23(3–4):107–17.CrossRefPubMedGoogle Scholar
  25. 25.
    Hagberg B. Rett syndrome: Clinical peculiarities and biological mysteries. Acta Paediatr. 1995;84(9):971–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Urbanowicz A, Leonard H, Girdler S, Ciccone N, Downs J. Parental perspectives on the communication abilities of their daughters with Rett syndrome. Dev Neurorehabil. 2016;19(1):17–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Townend GS, Marschik PB, Smeets E, van de Berg R, van den Berg M, Curfs LM. Eye gaze technology as a form of augmentative and alternative communication for individuals with Rett syndrome: Experiences of families in the Netherlands. J Dev Phys Disabil. 2016;28:101–12.CrossRefPubMedGoogle Scholar
  28. 28.
    Lotan M, Isakov E, Merrick J. Improving functional skills and physical fitness in children with Rett syndrome. J Intellect Disabil Res. 2004;48(8):730–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Lotan M, Schenker R, Wine J, Downs J. The conductive environment enhances gross motor function of girls with Rett syndrome. A pilot study. Dev Neurorehabil. 2012;15(1):19–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Epstein A, Leonard H, Davis E, Williams K, Reddihough D, Murphy N, et al. Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods. Am J Med Genet A. 2015; doi: 10.1002/ajmg.a.37500.PubMedGoogle Scholar
  31. 31.
    Tarquinio DC, Motil KJ, Hou W, Lee H‑S, Glaze DG, Skinner SA, et al. Growth failure and outcome in Rett syndrome specific growth references. Neurology. 2012;79(16):1653–61.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Motil KJ, Caeg E, Barrish JO, Geerts S, Lane JB, Percy AK, et al. Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett syndrome. J Pediatr Gastroenterol Nutr. 2012;55(3):292–8.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Julu PO, Kerr AM, Apartopoulos F, Al-Rawas S, Witt Engerstrom I, Engerstrom L, et al. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child. 2001;85(1):29–37.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Wong K, Leonard H, Jacoby P, Ellaway C, Downs J. The trajectories of sleep disturbances in Rett syndrome. J Sleep Res. 2014; doi: 10.1111/jsr.12240.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Downs J, Bebbington A, Woodhead H, Jacoby P, Jian L, Jefferson A, et al. Early determinants of fractures in Rett syndrome. Pediatrics. 2008;121(3):540–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Downs J, Geranton S, Bebbington A, Jacoby P, Bahi-Buisson N, Ravine D, et al. Linking MECP2 and pain sensitivity: The example of Rett syndrome. Am J Med Genet A. 2010; doi: 10.1002/ajmg.a.33314.Google Scholar
  37. 37.
    Symons FJ, Byiers B, Tervo RC, Beisang A. Parent-reported pain in Rett syndrome. Clin J Pain. 2013;29(8):744–6.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Regnard C, Reynolds J, Watson B, Matthews D, Gibson L, Clarke C. Understanding distress in people with severe communication difficulties: Developing and assessing the Disability Distress Assessment Tool (DisDAT). J Intellect Disabil Res. 2007;51(Pt 4):277–92.CrossRefPubMedGoogle Scholar
  39. 39.
    Marr C, Leonard H, Torode I, Downs J. Spinal fusion in girls with Rett syndrome: Post-operative recovery and family experiences. Child Care Health Dev. 2015; doi: 10.1111/cch.12243.PubMedGoogle Scholar
  40. 40.
    Downs J, Bergman A, Carter P, Anderson A, Palmer GM, Roye D, et al. Guidelines for management of scoliosis in Rett syndrome patients based on expert consensus and clinical evidence. Spine. 2009;34(17):E607–E617.CrossRefPubMedGoogle Scholar
  41. 41.
    Baikie G, Ravikumara M, Downs J, Naseem N, Wong K, Percy A, et al. Gastrointestinal dysmotility in rett syndrome. J Pediatr Gastroenterol Nutr. 2014;58(2):244–51.CrossRefGoogle Scholar
  42. 42.
    Leonard H, Ravikumar M, Baikie G, Naseem N, Ellaway C, Percy A, et al. Assessment and management of nutrition and growth in Rett syndrome. J Pediatr Gastroenterol Nutr. 2013;57(4):451–60.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Jefferson A, Leonard H, Siafarikas A, Woodhead H, Fyfe S, Ward LM, et al. Clinical guidelines for management of bone health in Rett syndrome based on expert consensus and available evidence. PLoS ONE. 2016;11(2):e0146824.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Verdugo MA, Schalock RL, Keith KD, Stancliffe RJ. Quality of life and its measurement: Important principles and guidelines. J Intellect Disabil Res. 2005;49(10):707–17.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Telethon Kids InstituteThe University of Western AustraliaWest PerthAustralia
  2. 2.School of Physiotherapy and Exercise Science, Faculty of Health SciencesCurtin UniversityPerthAustralia

Personalised recommendations