title: Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis.
abstract: OBJECTIVE
  Diagnosis of Rett syndrome (RTT) is often delayed. We sought to determine the type of physician who typically makes the RTT diagnosis and to identify risk factors for delayed diagnosis.
  
  
  METHODS
  A total of 1085 participants from the multicenter longitudinal RTT natural history study with classic and atypical RTT were recruited between 2006 and 2014. Age of diagnosis, diagnostician, diagnostic criteria, and clinical and developmental data were collected.
  
  
  RESULTS
  Among 919 classic and 166 atypical RTT participants, the median diagnosis age was 2.7 years (interquartile range 2.0-4.1) in classic and 3.8 years (interquartile range 2.3-6.9) in atypical RTT. Pediatricians made the diagnosis of classic RTT rarely (5.2%); however, the proportion diagnosed by pediatricians has increased since 2006. Since the first diagnostic criteria, the age of diagnosis decreased among subspecialists but not pediatricians. Odds of a pediatrician making the diagnosis of classic RTT were higher if a child stopped responding to parental interaction, and lower if they possessed gastroesophageal reflux, specific stereotypies, lost babbling, or the ability to follow commands. Delayed acquisition of basic gross motor skills or finger feeding was associated with younger diagnosis; delayed acquisition of higher level fine motor skills, later onset of supportive features, and normal head circumference were associated with late diagnosis. Thirty-three percent with microcephaly before 2.5 years were diagnosed after the median age of 2.7 years.
  
  
  CONCLUSIONS
  Age of RTT diagnosis has improved among subspecialists, and pediatricians have made the diagnosis of classic RTT more frequently since 2006. Strategies for educating diagnosticians should incorporate specific risk factors for delayed diagnosis.
authors: Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia. Electronic address: Daniel.tarquinio@emory.edu.
authors: Daniel C
authors: DC
authors: Tarquinio
authors: Stony Brook University Medical Center, Stony Brook, New York.
authors: Wei
authors: W
authors: Hou
authors: Rady Children's Hospital, University of California, San Diego, California.
authors: Jeffrey L
authors: JL
authors: Neul
authors: University of Alabama at Birmingham, Alabama.
authors: Jane B
authors: JB
authors: Lane
authors: Boston Children's Hospital, Boston, Massachusetts.
authors: Katherine V
authors: KV
authors: Barnes
authors: Boston Children's Hospital, Boston, Massachusetts.
authors: Heather M
authors: HM
authors: O'Leary
authors: Boston Children's Hospital, Boston, Massachusetts.
authors: Natalie M
authors: NM
authors: Bruck
authors: Boston Children's Hospital, Boston, Massachusetts.
authors: Walter E
authors: WE
authors: Kaufmann
authors: Baylor College of Medicine, Houston, Texas.
authors: Kathleen J
authors: KJ
authors: Motil
authors: Baylor College of Medicine, Houston, Texas.
authors: Daniel G
authors: DG
authors: Glaze
authors: Greenwood Genetic Center, Greenwood, South Carolina.
authors: Steven A
authors: SA
authors: Skinner
authors: Greenwood Genetic Center, Greenwood, South Carolina.
authors: Fran
authors: F
authors: Annese
authors: Greenwood Genetic Center, Greenwood, South Carolina.
authors: Lauren
authors: L
authors: Baggett
authors: Baylor College of Medicine, Houston, Texas.
authors: Judy O
authors: JO
authors: Barrish
authors: University of Alabama at Birmingham, Alabama.
authors: Suzanne P
authors: SP
authors: Geerts
authors: University of Alabama at Birmingham, Alabama.
authors: Alan K
authors: AK
authors: Percy
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D057210:Delayed Diagnosis; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015518:Rett Syndrome / Q000175:diagnosis*; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
keywords: MECP2; Rett syndrome; early diagnosis; prognosis; risk factors