Abstract
Modifications to diagnostic criteria and introduction of genetic testing have likely affected the pattern and timing of Rett syndrome diagnosis. The trends in incidence and prevalence of Rett syndrome in Australia were examined; the cumulative risk of a female being diagnosed was determined; and the impact of changes to diagnostic criteria and availability of genetic testing on these frequencies was investigated. The population-based Australian Rett Syndrome Database was used to identify a total of 349 verified Rett syndrome females born 1976–2006 and diagnosed 1982–2008. The proportion of female cases born and diagnosed per year and the cumulative risk of a diagnosis were determined. The median age of Rett syndrome diagnosis decreased from 4.5 y if diagnosed before 2000 to 3.5 y if diagnosed after 1999. The cumulative risk of diagnosis had almost doubled by 32 y of age [1/8,905 or 11.23 per 100,000 person-years (95% CI, 10.03–12.45)] in comparison with 5 y of age [1/15,361 or 6.51 per 100,000 person-years (95% CI, 5.65–7.39)]. Earlier age of diagnosis may result in families experiencing less stress and emotional strain compared with those with delayed diagnosis.
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Abbreviations
- APSU:
-
Australian Paediatric Surveillance Unit
- ARSD:
-
Australian Rett Syndrome Database
- ERP:
-
Estimated Residential Population
- MECP2 :
-
Methyl-CpG Binding Protein 2
- RTT:
-
Rett Syndrome
References
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. Ann Neurol 14: 471–479
Hagberg B, Goutieres F, Hanefield F, Rett A, Wilson J 1985 Rett Syndrome: criteria for inclusion and exclusion. Brain Dev 7: 372–373
Naidu S, Murphy M, Moser HW, Rett A 1986 Rett syndrome—natural history in 70 cases. Am J Med Genet Suppl 1: 61–72
Hagberg B, Witt-Engerström I 1986 Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl 1: 47–59
Trevathan E, Moser HW 1988 Diagnostic criteria for Rett syndrome. The Rett Syndrome Diagnostic Criteria Work Group. Ann Neurol 23: 425–428
Hagberg BA 1994 Rett variants: a suggested model for inclusion criteria. Pediatr Neurol 11: 5–11
Ariani F, Hayek G, Rondinella D, Artuso R, Mencarelli MA, Spanhol-Rosseto A, Pollazzon M, Buoni S, Spiga O, Ricciardi S, Meloni I, Longo I, Mari F, Broccoli V, Zappella M, Renieri A 2008 FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 83: 89–93
Zappella M, Gillberg C, Ehlers S 1998 The preserved speech variant: a subgroup of the Rett complex: a clinical report of 30 cases. J Autism Dev Disord 28: 519–526
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY 1999 Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23: 185–188
Hagberg B, Hanefeld F, Percy AK, Skjeldal OH 2002 An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett syndrome clinical criteria consensus panel satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, September 11, 2001. Eur J Paediatr Neurol 6: 293–297
Erlandson A, Samuelsson L, Hagberg B, Kyllerman M, Vujic M, Wahlstrom J 2003 Multiplex ligation-dependent probe amplification (MLPA) detects large deletions in the MECP2 gene of Swedish Rett syndrome patients. Genet Test 7: 329–332
Amir RE, Fang P, Yu Z, Glaze DG, Percy AK, Zoghbi HY, Roa BB, Van den Veyver IB 2005 Mutations in exon 1 of MECP2 are a rare cause of Rett syndrome. J Med Genet 42: e15
Bienvenu T, Philippe C, De Roux N, Raynaud M, Bonnefond JP, Pasquier L, Lesca G, Mancini J, Jonveaux P, Moncla A, Feingold J, Chelly J, Villard L 2006 The incidence of Rett syndrome in France. Pediatr Neurol 34: 372–375
Boltshauser E, Kunzle C 1987 Prevalence of Rett syndrome in Switzerland. Helv Paediatr Acta 42: 407–411
Burd L, Vesley B, Martsolf JT, Kerbeshian J 1991 Prevalence study of Rett syndrome in North Dakota children. Am J Med Genet 38: 565–568
Hagberg B 1985 Rett's syndrome: prevalence and impact on progressive severe mental retardation in girls. Acta Paediatr Scand 74: 405–408
Hagberg B, Witt-Engerström I 1987 Rett syndrome: epidemiology and nosology—progress in knowledge 1986—a conference communication. Brain Dev 9: 451–457
Kerr AM, Stephenson JB 1985 Rett's syndrome in the west of Scotland. BMJ (Clin Res Ed) 291: 579–582
Kozinetz CA, Skender ML, MacNaughton N, Almes MJ, Schultz RJ, Percy AK, Glaze DG 1993 Epidemiology of Rett syndrome: a population-based registry. Pediatrics 91: 445–450
Laurvick CL, de Klerk N, Bower C, Christodoulou J, Ravine D, Ellaway C, Williamson S, Leonard H 2006 Rett syndrome in Australia: a review of the epidemiology. J Pediatr 148: 347–352
Leonard H, Bower C, English D 1997 The prevalence and incidence of Rett syndrome in Australia. Eur Child Adolesc Psychiatry 6: 8–10
Pini G, Milan M, Zappella M 1996 Rett syndrome in Northern Tuscany (Italy): family tree studies. Clin Genet 50: 486–490
Skjeldal OH, Vontetzchner S, Aspelund F, Herder GA, Lofterod B 1997 Rett syndrome—geographic variation in prevalence in Norway. Brain Dev 19: 258–261
Suzuki H, Hirayama Y, Arima M 1989 [Prevalence of Rett syndrome in Tokyo]. No To Hattatsu 21: 430–433
Talvik T, Soot A, Beilmann A, Soopld T, Nurk K 1995 Rett syndrome in Estonia: prevalence of the classical phenotype. Acta Paediatr 84: 1070–1071
Terai K, Munesue T, Hiratani M, Jiang ZY, Jibiki I, Yamaguchi N 1995 The prevalence of Rett syndrome in Fukui prefecture. Brain Dev 17: 153–154
Wong VC, Li SY 2007 Rett syndrome: prevalence among Chinese and a comparison of MECP2 mutations of classic Rett syndrome with other neurodevelopmental disorders. J Child Neurol 22: 1397–1400
Zappella M, Cerioli M 1987 High prevalence of Rett syndrome in a small area. Brain Dev 9: 479–480
Elliott EJ, Chant KG 1994 Rare disease surveillance. J Paediatr Child Health 30: 463–465
He S, Zurynski YA, Elliott EJ 2009 Evaluation of a national resource to identify and study rare diseases: the Australian Paediatric Surveillance Unit. J Paediatr Child Health 45: 498–504
Zurynski Y, Davey E, Elliot EJ 2010 Australian Paediatric Surveillance Unit annual report, 2008 and 2009. Commun Dis Intell 34: 285–290
Srikanthan S, Zurynski Y, Elliott E 2008 APSU Australian Paediatric Surveillance Unit: Celebrating 15 Years of Surveillance 1993–2007. Australian Paediatric Surveillance Unit, Westmead,
Nassar N, Dixon G, Bourke J, Bower C, Glasson E, de Klerk N, Leonard H 2009 Autism spectrum disorders in young children: effect of changes in diagnostic practices. Int J Epidemiol 38: 1245–1254
Rothman KJ, Greenland S, Lash TL 2008 Modern Epidemiology. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, p 47
Australian Bureau of Statistics 3105.0.65.001 Australian historical population statistics, 2006, Table 36. Available at: http://www.abs.gov.au/AUSSTATS/abs@.nsf/DetailsPage/3105.0.65.0012006?OpenDocument. Accessed October 20, 2009
Australian Bureau of Statistics 2007.3301.0 Births, Australia, 2007, Table 1. Available at: http://www.abs.gov.au/AUSSTATS/abs@.nsf/DetailsPage/3301.02007?OpenDocument. Accessed October 20, 2009
Australian Bureau of Statistics 2009 3201.0 Population by age and sex, Australian states and territories, Table 9.1. Available at: http://www.abs.gov.au/AUSSTATS/abs@.nsf/DetailsPage/3201.0Jun%202008?OpenDocument. Accessed October 20, 2009
Kaplan EL, Meier P 1958 Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
Fehr S, Downs J, Bebbington A, Leonard H 2010 Atypical presentations and specific genotypes are associated with a delay in diagnosis in diagnosis in females with Rett syndrome. Am J Med Genet A 152: 2535–2542
Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK, RettSearch Consortium 2010 Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol 68: 944–950
Last JM, Spasoff RA, Harris SS, Thuriaux MC, International Epidemiological Association 2001 A Dictionary of Epidemiology. Oxford University Press, New York,
Bebbington A, Anderson A, Ravine D, Fyfe S, Pineda M, de Klerk N, Ben-Zeev B, Yatawara N, Percy AK, Kaufmann WE, Leonard H 2008 Investigating genotype-phenotype relationships in Rett syndrome using an international dataset. Neurology 70: 868–875
Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N 2005 CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 14: 1935–1946
Graungaard AH, Skov L 2007 Why do we need a diagnosis? A qualitative study of parents' experiences, coping and needs, when the newborn child is severely disabled. Child Care Health Dev 33: 296–307
European Organisation for Rare Diseases 2005 Rare diseases: understanding this public health priority. Available at: http://www.eurordis.org/IMG/pdf/princeps_document-EN.pdf. Accessed March 18, 2009
Acknowledgements
We thank the families who have participated in the Australian Rett syndrome study. We also gratefully acknowledge the clinicians who completed questionnaires and extend our gratitude to the Australian Pediatric Surveillance Unit (APSU) and the Australian Rett syndrome Association for their ongoing support in case ascertainment in Australia.
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Supported by the National Institute of Health grant 5R01HD043100-05, NHMRC #303189. H.L. was previously funded by a NHMRC program grant (#353514) and current funding is from an NHMRC Senior Research Fellowship #572568. N.N. is funded by a NHMRC Career Development Award (#632955).
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Fehr, S., Bebbington, A., Nassar, N. et al. Trends in the Diagnosis of Rett Syndrome in Australia. Pediatr Res 70, 313–319 (2011). https://doi.org/10.1203/PDR.0b013e3182242461
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DOI: https://doi.org/10.1203/PDR.0b013e3182242461
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