@article{d68d9c61167f4be8a6727b6f33fe8b83,
title = "Age of diagnosis in rett syndrome: Patterns of recognition among diagnosticians and risk factors for late diagnosis",
abstract = "Purpose 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.",
keywords = "MECP2, Rett syndrome, early diagnosis, prognosis, risk factors",
author = "Tarquinio, {Daniel C.} and Wei Hou and Neul, {Jeffrey L.} and Lane, {Jane B.} and Barnes, {Katherine V.} and O'Leary, {Heather M.} and Bruck, {Natalie M.} and Kaufmann, {Walter E.} and Motil, {Kathleen J.} and Glaze, {Daniel G.} and Skinner, {Steven A.} and Fran Annese and Lauren Baggett and Barrish, {Judy O.} and Geerts, {Suzanne P.} and Percy, {Alan K.}",
note = "Funding Information: Drs. Tarquinio and Percy had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Support for design and conduct of the study, as well as collection, management, analysis, and interpretation of the data are provided by grants from the International Rett Syndrome Foundation and from the National Institutes of Health (NIH), including the Angelman, Rett, Prader-Willi syndrome consortium ( U54HD61222 ) a part of the NIH Rare Disease Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS) and the Eunice Kennedy Shriver Child Health and Human Development Institute . Also supported by NIH U54 grants RR019478 (NCRR) and HD061222 (NICHD), and IDDRC grant HD38985 (NICHD), funds from the International Rett Syndrome Foundation and Civitan International Research Center . Trial Registration is at clinicaltrials.gov ; Identifier: NCT00299. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Navah Kadish and Karen Pepper for thoughtful review of the manuscript, and Eric Pedrotty for computation of socioeconomic data, all of whom gave written permission for such acknowledgment. JLN, JBL, DGG, and AKP are funded by Neuren Pharmaceuticals . The remaining authors have no financial relationships relevant to this article to disclose. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jun,
day = "1",
doi = "10.1016/j.pediatrneurol.2015.02.007",
language = "English (US)",
volume = "52",
pages = "585--591.e2",
journal = "Pediatric Neurology",
issn = "0887-8994",
publisher = "Elsevier Inc.",
number = "6",
}