Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Rett syndrome: Genetics, clinical features, and diagnosis

Rebecca J Schultz, PhD, RN, CPNP
Daniel G Glaze, MD
Section Editors
Marc C Patterson, MD, FRACP
Helen V Firth, DM, FRCP, DCH
Deputy Editor
John F Dashe, MD, PhD


Rett syndrome (RTT) is a neurodevelopmental disorder that occurs almost exclusively in females. It was described in 1966 by Andreas Rett, an Austrian pediatrician and neurologist [1]. After a brief period of initially normal development, affected patients experience loss of speech and purposeful hand use, stereotypic hand movements, and gait abnormalities. Additional features include deceleration of head growth, seizures, autistic features, and breathing abnormalities [2]. Most cases result from mutations in the MECP2 gene [3].

This topic will review the genetics, clinical features, and diagnosis of Rett syndrome. The treatment and prognosis are reviewed elsewhere. (See "Rett syndrome: Treatment and prognosis".)

Autism spectrum disorders are discussed separately. (See "Autism spectrum disorder: Terminology, epidemiology, and pathogenesis" and "Autism spectrum disorder: Clinical features" and "Autism spectrum disorder: Diagnosis".)


In the majority of patients, RTT is caused by mutations in the MECP2 gene, which maps to Xq28 and encodes methyl-CpG binding protein 2 (MeCP2) [3]. Although MeCP2 is expressed in all tissues, it is most abundant in the brain, which may be more sensitive to abnormal MeCP2 than other tissues. Mutations in MECP2 have been detected in approximately 95 percent of classic sporadic RTT cases and 75 percent of atypical RTT cases [4,5]. A minority of patients have atypical RTT caused by mutations in CDLK5 or FOXG1 genes. (See 'Classification and major features' below and 'Atypical RTT' below.)

Three types of MECP2 mutations occur: missense, frameshift, and nonsense. The type of mutation may affect phenotypic expression. (See 'Genotype-phenotype correlations' below.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Feb 02, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Rett A. [On a unusual brain atrophy syndrome in hyperammonemia in childhood]. Wien Med Wochenschr 1966; 116:723.
  2. Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol 2010; 68:944.
  3. Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999; 23:185.
  4. Percy AK, Lane JB, Childers J, et al. Rett syndrome: North American database. J Child Neurol 2007; 22:1338.
  5. Neul JL, Fang P, Barrish J, et al. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 2008; 70:1313.
  6. Percy AK, Neul JL, Glaze DG, et al. Rett syndrome diagnostic criteria: lessons from the Natural History Study. Ann Neurol 2010; 68:951.
  7. Trappe R, Laccone F, Cobilanschi J, et al. MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet 2001; 68:1093.
  8. Cheadle JP, Gill H, Fleming N, et al. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet 2000; 9:1119.
  9. Wan M, Lee SS, Zhang X, et al. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 1999; 65:1520.
  10. Orrico A, Lam C, Galli L, et al. MECP2 mutation in male patients with non-specific X-linked mental retardation. FEBS Lett 2000; 481:285.
  11. Meloni I, Bruttini M, Longo I, et al. A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males. Am J Hum Genet 2000; 67:982.
  12. Villard L, Kpebe A, Cardoso C, et al. Two affected boys in a Rett syndrome family: clinical and molecular findings. Neurology 2000; 55:1188.
  13. Allen RC, Zoghbi HY, Moseley AB, et al. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 1992; 51:1229.
  14. Clayton-Smith J, Watson P, Ramsden S, Black GC. Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males. Lancet 2000; 356:830.
  15. Moog U, Van Roozendaal K, Smeets E, et al. MECP2 mutations are an infrequent cause of mental retardation associated with neurological problems in male patients. Brain Dev 2006; 28:305.
  16. Ohki I, Shimotake N, Fujita N, et al. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell 2001; 105:487.
  17. Castro J, Mellios N, Sur M. Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome. Curr Opin Neurol 2013; 26:154.
  18. Díaz de León-Guerrero S, Pedraza-Alva G, Pérez-Martínez L. In sickness and in health: the role of methyl-CpG binding protein 2 in the central nervous system. Eur J Neurosci 2011; 33:1563.
  19. Buchovecky CM, Turley SD, Brown HM, et al. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. Nat Genet 2013; 45:1013.
  20. Percy AK. Neuroscience. Path to treat Rett syndrome. Science 2013; 342:318.
  21. Colvin L, Leonard H, de Klerk N, et al. Refining the phenotype of common mutations in Rett syndrome. J Med Genet 2004; 41:25.
  22. Bebbington A, Anderson A, Ravine D, et al. Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology 2008; 70:868.
  23. Pidcock FS, Salorio C, Bibat G, et al. Functional outcomes in Rett syndrome. Brain Dev 2016; 38:76.
  24. Archer H, Evans J, Leonard H, et al. Correlation between clinical severity in patients with Rett syndrome with a p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X-chromosome inactivation. J Med Genet 2007; 44:148.
  25. Cuddapah VA, Pillai RB, Shekar KV, et al. Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. J Med Genet 2014; 51:152.
  26. Brown K, Selfridge J, Lagger S, et al. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome. Hum Mol Genet 2016; 25:558.
  27. Zhang Y, Minassian BA. Will my Rett syndrome patient walk, talk, and use her hands? Neurology 2008; 70:1302.
  28. Armstrong DD, Dunn JK, Schultz RJ, et al. Organ growth in Rett syndrome: a postmortem examination analysis. Pediatr Neurol 1999; 20:125.
  29. Jellinger K, Armstrong D, Zoghbi HY, Percy AK. Neuropathology of Rett syndrome. Acta Neuropathol 1988; 76:142.
  30. Casanova MF, Naidu S, Goldberg TE, et al. Quantitative magnetic resonance imaging in Rett syndrome. J Neuropsychiatry Clin Neurosci 1991; 3:66.
  31. Reiss AL, Faruque F, Naidu S, et al. Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol 1993; 34:227.
  32. Armstrong DD. Review of Rett syndrome. J Neuropathol Exp Neurol 1997; 56:843.
  33. Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 1995; 45:1581.
  34. Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005; 20:747.
  35. Armstrong D, Dunn JK, Antalffy B, Trivedi R. Selective dendritic alterations in the cortex of Rett syndrome. J Neuropathol Exp Neurol 1995; 54:195.
  36. Kaufmann WE, Naidu S, Budden S. Abnormal expression of microtubule-associated protein 2 (MAP-2) in neocortex in Rett syndrome. Neuropediatrics 1995; 26:109.
  37. Kaufmann WE, Taylor CV, Hohmann CF, et al. Abnormalities in neuronal maturation in Rett syndrome neocortex: preliminary molecular correlates. Eur Child Adolesc Psychiatry 1997; 6 Suppl 1:75.
  38. Kozinetz CA, Skender ML, MacNaughton N, et al. Epidemiology of Rett syndrome: a population-based registry. Pediatrics 1993; 91:445.
  39. Bienvenu T, Philippe C, De Roux N, et al. The incidence of Rett syndrome in France. Pediatr Neurol 2006; 34:372.
  40. Hagberg B. Rett's syndrome: prevalence and impact on progressive severe mental retardation in girls. Acta Paediatr Scand 1985; 74:405.
  41. Kerr AM, Stephenson JB. Rett's syndrome in the west of Scotland. Br Med J (Clin Res Ed) 1985; 291:579.
  42. Leonard H, Bower C, English D. The prevalence and incidence of Rett syndrome in Australia. Eur Child Adolesc Psychiatry 1997; 6 Suppl 1:8.
  43. Hagberg B, Witt-Engerström I. Rett syndrome: epidemiology and nosology--progress in knowledge 1986--a conference communication. Brain Dev 1987; 9:451.
  44. Einspieler C, Kerr AM, Prechtl HF. Is the early development of girls with Rett disorder really normal? Pediatr Res 2005; 57:696.
  45. Fehr S, Bebbington A, Ellaway C, et al. Altered attainment of developmental milestones influences the age of diagnosis of rett syndrome. J Child Neurol 2011; 26:980.
  46. Hagberg G, Stenbom Y, Witt Engerström I. Head growth in Rett syndrome. Acta Paediatr 2000; 89:198.
  47. Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol 1983; 14:471.
  48. Hagberg B, Hanefeld F, Percy A, Skjeldal O. 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, 11 September 2001. Eur J Paediatr Neurol 2002; 6:293.
  49. Zappella M. The Rett girls with preserved speech. Brain Dev 1992; 14:98.
  50. Renieri A, Mari F, Mencarelli MA, et al. Diagnostic criteria for the Zappella variant of Rett syndrome (the preserved speech variant). Brain Dev 2009; 31:208.
  51. Artuso R, Mencarelli MA, Polli R, et al. Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria. Brain Dev 2010; 32:17.
  52. Scala E, Ariani F, Mari F, et al. CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J Med Genet 2005; 42:103.
  53. Evans JC, Archer HL, Colley JP, et al. Early onset seizures and Rett-like features associated with mutations in CDKL5. Eur J Hum Genet 2005; 13:1113.
  54. Bahi-Buisson N, Nectoux J, Rosas-Vargas H, et al. Key clinical features to identify girls with CDKL5 mutations. Brain 2008; 131:2647.
  55. Russo S, Marchi M, Cogliati F, et al. Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes. Neurogenetics 2009; 10:241.
  56. Ariani F, Hayek G, Rondinella D, et al. FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 2008; 83:89.
  57. Mencarelli MA, Spanhol-Rosseto A, Artuso R, et al. Novel FOXG1 mutations associated with the congenital variant of Rett syndrome. J Med Genet 2010; 47:49.
  58. Philippe C, Amsallem D, Francannet C, et al. Phenotypic variability in Rett syndrome associated with FOXG1 mutations in females. J Med Genet 2010; 47:59.
  59. Reichow B, George-Puskar A, Lutz T, et al. Brief report: systematic review of Rett syndrome in males. J Autism Dev Disord 2015; 45:3377.
  60. Sigafoos J, van der Meer L, Kagohara D, et al. Communication assessment for individuals with Rett syndrome: A systematic review. Res Autism Spectr Disord 2011; 5:692.
  61. Temudo T, Oliveira P, Santos M, et al. Stereotypies in Rett syndrome: analysis of 83 patients with and without detected MECP2 mutations. Neurology 2007; 68:1183.
  62. FitzGerald PM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord 1990; 5:195.
  63. Colvin L, Fyfe S, Leonard S, et al. Describing the phenotype in Rett syndrome using a population database. Arch Dis Child 2003; 88:38.
  64. Ager S, Fyfe S, Christodoulou J, et al. Predictors of scoliosis in Rett syndrome. J Child Neurol 2006; 21:809.
  65. Percy AK, Lee HS, Neul JL, et al. Profiling scoliosis in Rett syndrome. Pediatr Res 2010; 67:435.
  66. Downs J, Torode I, Wong K, et al. The Natural History of Scoliosis in Females With Rett Syndrome. Spine (Phila Pa 1976) 2016; 41:856.
  67. Tarquinio DC, Motil KJ, Hou W, et al. Growth failure and outcome in Rett syndrome: specific growth references. Neurology 2012; 79:1653.
  68. Schultz R, Glaze D, Motil K, et al. Hand and foot growth failure in Rett syndrome. J Child Neurol 1998; 13:71.
  69. Leonard H, Ravikumara M, Baikie G, et al. Assessment and management of nutrition and growth in Rett syndrome. J Pediatr Gastroenterol Nutr 2013; 57:451.
  70. Motil KJ, Schultz RJ, Wong WW, Glaze DG. Increased energy expenditure associated with repetitive involuntary movement does not contribute to growth failure in girls with Rett syndrome. J Pediatr 1998; 132:228.
  71. Motil KJ, Schultz R, Brown B, et al. Altered energy balance may account for growth failure in Rett syndrome. J Child Neurol 1994; 9:315.
  72. Motil KJ, Schultz RJ, Glaze DG. Dietary energy supplementation reverses cranial, linear, and ponderal growth failure in girls with Rett syndrome. Pediatr Res 1996; 39:378A.
  73. Motil KJ, Schultz RJ, Kertz B, et al. Increased body protein degradation is associated with lean body mass deficits in girls with Rett syndrome. FASEB J 1999; 13:A9.
  74. Motil KJ, Morrissey M, Caeg E, et al. Gastrostomy placement improves height and weight gain in girls with Rett syndrome. J Pediatr Gastroenterol Nutr 2009; 49:237.
  75. Morton RE, Bonas R, Minford J, et al. Feeding ability in Rett syndrome. Dev Med Child Neurol 1997; 39:331.
  76. Budden SS. Management of Rett syndrome: a ten year experience. Neuropediatrics 1995; 26:75.
  77. Rice MA, Haas RH. The nutritional aspects of Rett syndrome. J Child Neurol 1988; 3 Suppl:S35.
  78. Thommessen M, Heiberg A, Kase BF, et al. Feeding problems, height and weight in different groups of disabled children. Acta Paediatr Scand 1991; 80:527.
  79. Thommessen M, Kase BF, Heiberg A. Growth and nutrition in 10 girls with Rett syndrome. Acta Paediatr 1992; 81:686.
  80. Motil KJ, Schultz RJ, Browning K, et al. Oropharyngeal dysfunction and gastroesophageal dysmotility are present in girls and women with Rett syndrome. J Pediatr Gastroenterol Nutr 1999; 29:31.
  81. Motil KJ, Caeg E, Barrish JO, et al. Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett syndrome. J Pediatr Gastroenterol Nutr 2012; 55:292.
  82. Motil, KJ, Schultz, et al. Oropharyngeal dysfunction and upper gastrointestinal dysmotility, a reflection of disturbances in the autonomic nervous system in Rett syndrome. In: Rett Disorder and the Developing Brain, Kerr, A, Witt-Engerström, I (Eds), Oxford University Press, Oxford 2001. p.259.
  83. Dolce A, Ben-Zeev B, Naidu S, Kossoff EH. Rett syndrome and epilepsy: an update for child neurologists. Pediatr Neurol 2013; 48:337.
  84. Tarquinio DC, Hou W, Berg A, et al. Longitudinal course of epilepsy in Rett syndrome and related disorders. Brain 2017; 140:306.
  85. Glaze DG, Percy AK, Skinner S, et al. Epilepsy and the natural history of Rett syndrome. Neurology 2010; 74:909.
  86. Steffenburg U, Hagberg G, Hagberg B. Epilepsy in a representative series of Rett syndrome. Acta Paediatr 2001; 90:34.
  87. Glaze DG, Frost JD Jr, Zoghbi HY, Percy AK. Rett's syndrome: characterization of respiratory patterns and sleep. Ann Neurol 1987; 21:377.
  88. Kerr AM. Early clinical signs in the Rett disorder. Neuropediatrics 1995; 26:67.
  89. Glaze DG, Schultz RJ, Frost JD. Rett syndrome: characterization of seizures versus non-seizures. Electroencephalogr Clin Neurophysiol 1998; 106:79.
  90. Haas RH, Dixon SD, Sartoris DJ, Hennessy MJ. Osteopenia in Rett syndrome. J Pediatr 1997; 131:771.
  91. Motil KJ, Ellis KJ, Barrish JO, et al. Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome. Pediatr Res 2008; 64:435.
  92. Jefferson A, Fyfe S, Downs J, et al. Longitudinal bone mineral content and density in Rett syndrome and their contributing factors. Bone 2015; 74:191.
  93. Ellis KJ, Shypailo RJ, Hardin DS, et al. Z score prediction model for assessment of bone mineral content in pediatric diseases. J Bone Miner Res 2001; 16:1658.
  94. Leonard H, Thomson MR, Glasson EJ, et al. A population-based approach to the investigation of osteopenia in Rett syndrome. Dev Med Child Neurol 1999; 41:323.
  95. Downs J, Bebbington A, Woodhead H, et al. Early determinants of fractures in Rett syndrome. Pediatrics 2008; 121:540.
  96. Kerr AM, Armstrong DD, Prescott RJ, et al. Rett syndrome: analysis of deaths in the British survey. Eur Child Adolesc Psychiatry 1997; 6 Suppl 1:71.
  97. Sekul EA, Moak JP, Schultz RJ, et al. Electrocardiographic findings in Rett syndrome: an explanation for sudden death? J Pediatr 1994; 125:80.
  98. Driscoll DJ, Edwards WD. Sudden unexpected death in children and adolescents. J Am Coll Cardiol 1985; 5:118B.
  99. Acampa M, Guideri F. Cardiac disease and Rett syndrome. Arch Dis Child 2006; 91:440.
  100. Guideri F, Acampa M, Hayek G, et al. Reduced heart rate variability in patients affected with Rett syndrome. A possible explanation for sudden death. Neuropediatrics 1999; 30:146.
  101. Ellaway CJ, Sholler G, Leonard H, Christodoulou J. Prolonged QT interval in Rett syndrome. Arch Dis Child 1999; 80:470.
  102. Fuster-Siebert M, Castro-Gago M. Electrocardiographic findings in Rett syndrome. J Pediatr 1995; 126:506.
  103. Julu, POO. The Central Autonomic Disturbance in Rett Syndrome. In: Rett Disorder and the Developing Brain, Kerr, A, and Witt-Engerström, I (Eds). Oxford University Press, Oxford 2001. p.131.
  104. Weese-Mayer DE, Lieske SP, Boothby CM, et al. Autonomic dysregulation in young girls with Rett Syndrome during nighttime in-home recordings. Pediatr Pulmonol 2008; 43:1045.
  105. Deguchi K, Antalffy BA, Twohill LJ, et al. Substance P immunoreactivity in Rett syndrome. Pediatr Neurol 2000; 22:259.
  106. Matsuishi T, Nagamitsu S, Yamashita Y, et al. Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome. Ann Neurol 1997; 42:978.
  107. Smeets EE, Pelc K, Dan B. Rett Syndrome. Mol Syndromol 2012; 2:113.
  108. Glaze DG. Neurophysiology of Rett syndrome. J Child Neurol 2005; 20:740.
  109. Pini G, Bigoni S, Congiu L, et al. Rett syndrome: a wide clinical and autonomic picture. Orphanet J Rare Dis 2016; 11:132.
  110. Glaze DG, Frost JD Jr, Zoghbi HY, Percy AK. Rett's syndrome. Correlation of electroencephalographic characteristics with clinical staging. Arch Neurol 1987; 44:1053.
  111. Southall DP, Kerr AM, Tirosh E, et al. Hyperventilation in the awake state: potentially treatable component of Rett syndrome. Arch Dis Child 1988; 63:1039.
  112. Cirignotta F, Lugaresi E, Montagna P. Breathing impairment in Rett syndrome. Am J Med Genet Suppl 1986; 1:167.
  113. Marcus CL, Carroll JL, McColley SA, et al. Polysomnographic characteristics of patients with Rett syndrome. J Pediatr 1994; 125:218.
  114. Ogier M, Katz DM. Breathing dysfunction in Rett syndrome: understanding epigenetic regulation of the respiratory network. Respir Physiol Neurobiol 2008; 164:55.
  115. Ramirez JM, Ward CS, Neul JL. Breathing challenges in Rett syndrome: lessons learned from humans and animal models. Respir Physiol Neurobiol 2013; 189:280.
  116. Rohdin M, Fernell E, Eriksson M, et al. Disturbances in cardiorespiratory function during day and night in Rett syndrome. Pediatr Neurol 2007; 37:338.
  117. De Felice C, Guazzi G, Rossi M, et al. Unrecognized lung disease in classic Rett syndrome: a physiologic and high-resolution CT imaging study. Chest 2010; 138:386.
  118. Young D, Nagarajan L, de Klerk N, et al. Sleep problems in Rett syndrome. Brain Dev 2007; 29:609.
  119. Boban S, Wong K, Epstein A, et al. Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype. Am J Med Genet A 2016; 170:2292.
  120. Christodoulou, J, Ho, G. MECP2-related disorders. GeneReviews. http://www.ncbi.nlm.nih.gov/books/NBK1497/ (Accessed on September 09, 2015).
  121. Giesbers S, Didden R, Radstaake M, et al. Incontinence in Individuals with Rett Syndrome: A Comparative Study. J Dev Phys Disabil 2012; 24:287.
  122. Percy AK, Lane JB. Rett syndrome: model of neurodevelopmental disorders. J Child Neurol 2005; 20:718.
  123. Gold WA, Christodoulou J. The Utility of Next-Generation Sequencing in Gene Discovery for Mutation-Negative Patients with Rett Syndrome. Front Cell Neurosci 2015; 9:266.
  124. Lucariello M, Vidal E, Vidal S, et al. Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype. Hum Genet 2016; 135:1343.
  125. Hagberg B, Witt-Engerström I. Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl 1986; 1:47.
  126. Hagberg BA, Skjeldal OH. Rett variants: a suggested model for inclusion criteria. Pediatr Neurol 1994; 11:5.
  127. FitzGerald PM, Jankovic J, Glaze DG, et al. Extrapyramidal involvement in Rett's syndrome. Neurology 1990; 40:293.
  128. Tarquinio DC, Hou W, Neul JL, et al. Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis. Pediatr Neurol 2015; 52:585.
  129. Fehr S, Downs J, Bebbington A, Leonard H. Atypical presentations and specific genotypes are associated with a delay in diagnosis in females with Rett syndrome. Am J Med Genet A 2010; 152A:2535.
  130. Marangi G, Zollino M. Pitt-Hopkins Syndrome and Differential Diagnosis: A Molecular and Clinical Challenge. J Pediatr Genet 2015; 4:168.
  131. Peippo M, Ignatius J. Pitt-Hopkins Syndrome. Mol Syndromol 2012; 2:171.
  132. Dagli AI, Mueller J, Williams CA. Angelman syndrome. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1144/ (Accessed on September 16, 2016).
  133. Buiting K, Williams C, Horsthemke B. Angelman syndrome - insights into a rare neurogenetic disorder. Nat Rev Neurol 2016; 12:584.
  134. Lambert L, Bienvenu T, Allou L, et al. MEF2C mutations are a rare cause of Rett or severe Rett-like encephalopathies. Clin Genet 2012; 82:499.
  135. Allou L, Julia S, Amsallem D, et al. Rett-like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5-related disease. Clin Genet 2017; 91:431.