• Daniel Charles Tarquinio, Kathleen J Motil, Wei Hou, Hye-Seung Lee, Daniel G Glaze, Steven A Skinner, Jeff L Neul, Fran Annese, Lauren McNair, Judy O Barrish, Suzanne P Geerts, Jane B Lane, and Alan K Percy.
• Miami Children's Hospital, Miami, FL, USA. danieltarq@aol.com
• Neurology. 2012 Oct 16; 79 (16): 1653-61.

ObjectivesProminent growth failure typifies Rett syndrome (RTT). Our aims were to 1) develop RTT growth charts for clinical and research settings, 2) compare growth in children with RTT with that of unaffected children, and 3) compare growth patterns among RTT genotypes and phenotypes.MethodsA cohort of the RTT Rare Diseases Clinical Research Network observational study participants was recruited, and cross-sectional and longitudinal growth data and comprehensive clinical information were collected. A reliability study confirmed interobserver consistency. Reference curves for height, weight, head circumference, and body mass index (BMI), generated using a semiparametric model with goodness-of-fit tests, were compared with normative values using Student's t test adjusted for multiple comparisons. Genotype and phenotype subgroups were compared using analysis of variance and linear regression.ResultsGrowth charts for classic and atypical RTT were created from 9,749 observations of 816 female participants. Mean growth in classic RTT decreased below that for the normative population at 1 month for head circumference, 6 months for weight, and 17 months for length. Mean BMI was similar in those with RTT and the normative population. Pubertal increases in height and weight were absent in classic RTT. Classic RTT was associated with more growth failure than atypical RTT. In classic RTT, poor growth was associated with worse development, higher disease severity, and certain MECP2 mutations (pre-C-terminal truncation, large deletion, T158M, R168X, R255X, and R270X).ConclusionsRTT-specific growth references will allow effective screening for disease and treatment monitoring. Growth failure occurs less frequently in girls with RTT with better development, less morbidity typically associated with RTT, and late truncation mutations.

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