Article

Growth failure and outcome in Rett syndrome Specific growth references

and University of Alabama at Birmingham (S.G., J.L., A.K.P.).
Neurology (Impact Factor: 8.3). 10/2012; 79(16):1653-61. DOI: 10.1212/WNL.0b013e31826e9a70
Source: PubMed

ABSTRACT Prominent 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.
A 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.
Growth 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).
RTT-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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    • "Respiratory dysfunction on a clinical basis was categorized based on the corresponding Percy scale item (+ as minimal hyperventilation and/or apnea; ++ as intermittent hyperventilation and/or apnea; and +++ as hyperventilation and/or apnea with cyanosis) [41]. The corresponding í µí± §-scores for body weight, height, head circumference, and body mass index were calculated on the basis of validated RTT-specific growth charts [42]. Clinical stages distribution was: stage I (í µí±› = 4), stage II (í µí±› = 69), stage III (í µí±› = 92), and stage IV (í µí±› = 63). "
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    • "In this study, a total of 66 RTT patients (mean age 12.7 ± 9.1 years) with typical presentation and demonstrated MeCP2 mutation were enrolled (Table 1) [27]. RTT diagnosis and inclusion/exclusion criteria were based on the recently revised RTT nomenclature consensus [28] [29]. "
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    • "Most individuals with RTT have scoliosis, and some require surgical intervention (Percy et al., 2010). Nutrition and gastrointestinal function are also major clinical issues in RTT, and there is marked growth failure in most affected individuals (Tarquinio et al., 2012). It has long been recognized that head growth is impaired, resulting in acquired microcephaly (Hagberg et al., 1983), and height and weight are usually markedly diminished (Schultz et al., 1993). "
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