title: Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012.
abstract: OBJECTIVE
  Rett syndrome (RTT) is a neurodevelopmental disorder that affects mainly females; it results in multiple disabilities and carries a risk of medical comorbidities. Early diagnosis is important to help establish the best treatment opportunities and preventive care in order to slow down the progression of symptoms. We wanted to test our hypothesis that it is possible to diagnose RTT before the classical symptoms become obvious.
  
  
  METHODS
  We analysed development and symptoms before and at the time of the RTT diagnosis, as well as the symptoms that triggered MECP2 mutation analysis, in a cohort of girls with RTT born in Denmark between 2003 and 2012.
  
  
  RESULTS
  Twenty-four girls were included, and 87.5% of these girls were diagnosed when the classical RTT symptoms were recognized. However, parents were concerned about their daughters between 3 and 58 months prior to the RTT diagnosis, and they felt that the professionals did not share their concern in the beginning. When reviewing medical files and questionnaires, we noted that the majority of girls did have combinations of concerning symptoms such as developmental delay and a collection of subtle signs such as autistic traits, placidity, floppiness with suspicion of muscular or mitochondrial diseases, hair pulling, teeth grinding, development of incontinence and problems with initiating movements.
  
  
  CONCLUSIONS
  We conclude that many individuals with MECP2 mutation exhibit characteristics that should raise suspicion for RTT, prior to evolution of the core clinical criteria. As RTT is a rare disease, it is of importance to constantly educate clinicians for heightened awareness of RTT.
authors.affiliation: Centre for Rett Syndrome, Kennedy Centre, Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Gl. Landevej 7, 2600 Glostrup, Denmark. Electronic address: anne-marie.bisgaard.pedersen@regionh.dk.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bisgaard
authors.affiliation: Centre for Rett Syndrome, Kennedy Centre, Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Gl. Landevej 7, 2600 Glostrup, Denmark.
authors.forename: Bitten
authors.initials: B
authors.lastname: Schönewolf-Greulich
authors.affiliation: Molecular Genetic Laboratory, Department of Clinical Genetics, 4062, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Ravn
authors.affiliation: Department of Paediatrics, Roskilde Hospital, University of Copenhagen, Køgevej 7-13, 4000 Roskilde, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Rønde
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D002658:Developmental Disabilities / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D015518:Rett Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Early diagnosis; Intellectual disability (ID); MECP2; Regression; Rett syndrome (RTT); Symptoms