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.

Conflict of interest statement

Conflict of Interest: No authors have conflicts of interest to disclose.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure. Age of classic RTT diagnosis and diagnostician, based on historical period

FPO – VECTOR FILE IMAGES UPLOADED IN COLOR (FOR ONLINE-ONLY) AND B&W (FOR PRINT) VERSIONS Ages of diagnosis differed for subspecialists based on period, demonstrating a decline in age of diagnosis with stabilization after 2000. No significant trend was present for pediatricians. Post-hoc comparisons are detailed in Table 1. Box-plots indicate median age and inter-quartile range, and whiskers extend 1.5× the inter-quartile range. Ovals indicate outliers, and diamonds indicate extreme outliers. (To be reproduced in color on the Web and in black-and-white in print)