; Published online before print October 3, 2012; 2012;79;1653
Daniel Charles Tarquinio, Kathleen J. Motil, Wei Hou, et al.
Growth failure and outcome in Rett syndrome : Specific growth
January 2, 2013This information is current as of
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Growth failure and outcome in
Specific growth references
Kathleen J. Motil, MD,
Wei Hou, PhD
Hye-Seung Lee, PhD
Daniel G. Glaze, MD
Steven A. Skinner, MD
Jeff L. Neul, MD, PhD
Fran Annese, LMSW
Lauren McNair, MS,
Judy O. Barrish, BSN,
Suzanne P. Geerts, MS,
Jane B. Lane, BSN, RN
Alan K. Percy, MD
Objectives: 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
Methods: A cohort of the RTT Rare Diseases Clinical Research Network observational study par-
ticipants was recruited, and cross-sectional and longitudinal growth data and comprehensive
clinical information were collected. A reliability study confirmed interobserver consistency. Refer-
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.
Results: 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).
ANOVA ? analysis of variance; BMI ? body mass index; CSS ? Clinical Severity Score; EDF ? equivalent degrees of free-
dom; FDR ? false discovery rate; FOC ? fronto-occipital head circumference; MBA ? Motor Behavioral Assessment; non-
RTT ? participants possessing MECP2 mutation but without Rett syndrome; RNHS ? Rett Natural History Study; RTT ? Rett
Growth failure is a prominent feature in Rett syndrome (RTT); however, no RTT-specific
growth charts exist. Many comorbid disorders have an impact on growth in RTT, such as
oropharyngeal and gastrointestinal dysfunction, scoliosis, seizures, and osteopenia. The pattern
of growth in female patients with RTT trends well below the lowest centile on standard growth
references,1which fail to differentiate a normal RTT growth pattern from one caused by
malnutrition or illness.
Disease-specific standards screen for disease2–13and measure the effect of therapeutic inter-
ventions designed to improve nutrition and neurologic function.14,15With more than 200
mutation sites identified in the methyl-CpG-binding protein 2 gene (MECP2), the clinical
From the Miami Children’s Hospital (D.C.T.), Miami, FL; Baylor College of Medicine (K.J.M., D.G.G., J.L.N., J.O.B.), Houston, TX; University of
Florida (W.H.), Gainesville, FL; University of South Florida (H.-S.L.), Tampa, FL; Greenwood Genetic Center (S.A.S., F.A., L.M.), Greenwood, SC;
and University of Alabama at Birmingham (S.G., J.L., A.K.P.).
Study funding: Supported by NIH U54 grants RR019478 (National Center for Research Resources) and HD061222 (National Institute of Child
Health and Human Development [NICHD]), Intellectual and Developmental Disabilities Research Center grant HD38985 (NICHD), and funds
from the International Rett Syndrome Foundation and Civitan International Research Center.
Go to Neurology.org for full disclosures. Disclosures deemed relevant by the authors, if any, are provided at the end of this article.
Correspondence & reprint
requests to Dr. Tarquinio:
Copyright © 2012 by AAN Enterprises, Inc.
severity in RTT varies widely.16Associations
exist among specific mutations and functional
outcomes such as ambulation, hand use, and
language.17No study has generated accurate
RTT growth references or adequately examined
the associations between the degree of growth
failure and genotype or clinical severity.
The aim of this study was to develop RTT-
specific growth references for clinical and re-
search use. The secondary objectives were to
1) compare the patterns of growth between
patients with RTT and the normative popula-
tion and 2) examine the effects of secular
changes, disease severity, and MECP2 muta-
tion on growth.
METHODS Participants and data collection. Partici-
pants with classic RTT and atypical RTT and MECP2-positive
participants without clinical RTT (non-RTT) were recruited
from 2006 to 2011 through the multicenter RTT Natural His-
tory Study (RNHS) at 1 of 7 sites and evaluated every 6?12
months as described previously.18Diagnosis of classic and atypi-
cal RTT was based on consensus criteria19,20and was confirmed
by an RNHS neurologist or geneticist (D.G.G., J.L.N., A.K.P.,
S.A.S.). All participants had MECP2 testing; participants with
clinical RTT were included despite absence of a mutation. Eval-
uation included fronto-occipital head circumference (FOC),
weight, height, or length using standardized techniques, (appen-
dix e-1 on the Neurology®Web site at www.neurology.org) and 2
quantitative scales of developmental abilities and disease severity,
the Motor Behavioral Assessment (MBA) and Clinical Severity
Score (CSS) (appendix e-2). Interoperator and intraoperator re-
liability was excellent (within 3 mm or 0.3 kg). To analyze secu-
lar trends, supplemental retrospective data were collected for
participants seen by A.K.P. before the RNHS.
All female participants with classic and atypical RTT were
included. Male participants (n ? 20) were excluded, and non-
RTT female participants (n ? 31) were excluded from growth
chart construction because of the paucity of subjects but were
retained for comparison of adult measurements. No participants
were excluded based on premature birth or secondary medical
conditions; however, data on comorbidities were collected. Cor-
rected age was used for premature participants until 2 years of
age. A recruitment goal of 750 participants ensured at least 30
observations at standard visit intervals up to 18 years. Although
the age range of the charts extends to 18 years, data on individu-
als up to 25 years were included to attenuate the flaring “right-
edge effect” of data truncation on statistical smoothing.
Standard protocol approvals, registrations, and patient
consents. Institutional review board approval was obtained at
each institution-based site; informed assent was obtained from
participants’ families. The RNHS is registered as clinical trial
Statistical analysis. Data quality assurance. Data were
screened using exploratory data analysis (individual scatterplots,
boxplots, histograms, and quantile-quantile plots) to identify er-
roneous measurements and frequency at target ages. Erroneous
measurements were investigated through source documentation,
and unresolved errors were discarded. Measurements on scatter-
plots were discarded if they differed from interpolated values by
more than 2 kg for weight, 1 cm for FOC, or 2.5 cm for height;
1% were discarded.
Chart modeling. Charts for the 2nd, 9th, 25th, 50th, 75th,
91st, and 98th percentiles in classic and atypical RTT were cre-
ated using combined cross-sectional and longitudinal data.
Curves were modeled using LMS,21a semiparametric technique
that normalizes data using a power transformation (L) and sum-
marizes distribution based on median (M) and coefficient of
variation (S). After transformation, the mean and median are
equivalent. Values of L, M, and S are constrained to change
smoothly with age through penalized maximum likelihood. The
equivalent degrees of freedom (EDF) of curves for L, M, and S
were manipulated based on goodness-of-fit testing,22and EDF
values were adjusted to achieve empirical validity and biological
Chart comparisons. Charts were compared with normative
references using multiple t tests weekly for the first 3 months and
monthly thereafter. Adjustment was made using the false discov-
ery rate (FDR), the expected percentage of false predictions in a
set of predictions.23Because crossing 2 percentile lines (1.3 SDs)
is commonly considered abnormal growth velocity, the percent-
age of participants who did so was calculated. British normative
growth references were used because National Center for Health
Statistics charts do not include data for age older than 3 years for
FOC or younger than age 2 for body mass index (BMI).24
Charts were compared for RTT subgroups, including mild
and severe groups based on bimodal distribution of CSS and
MBA score. To study the effect of modern nutrition, secular
changes were compared in those born before vs after the median
year of birth (1997).
Genotype-phenotype and disease severity comparisons.
Common mutation type clustering reduced 148 MECP2 muta-
tions based on molecular similarities (common) into 8 common
point, pre-C-terminal truncating, C-terminal truncating, large
deletion, and other missense mutations (table 1). Measurements
were compared among each category using analysis of variance
(ANOVA) adjusted for multiple comparisons using the Tukey-
Kramer test. Growth velocity (from baseline to 6 years), time to
growth nadir, and measurements at key age ranges (0–2, 2–7,
7–12, 12–17, and ?17 years) were compared among different
The associations of the severity of common RTT character-
istics in childhood with adult measurements (?18 years old)
were examined using linear regression. Characteristics included
scoliosis severity (scoliosis), periodic breathing (hyperventila-
tion), repetitive hand movements (stereotypies), seizure severity
(seizure), ability to speak after regression (language) and commu-
nicate wants through nonverbal means (nonverbal), and age at
which the following occurred or were acquired: hand use, ambu-
lation, sitting unsupported (sitting), and regression of verbal and
motor skills (regression). Puberty onset based on Tanner staging
was compared with race-specific standards.25Associations of age
of pubertal onset with growth, RTT characteristics, and geno-
types were examined. Patients were categorized based on propor-
tion of FOC to somatic size. Associations of these proportions
with diagnoses, secular trends, RTT characteristics, genotype,
and pubertal onset were examined using ANOVA.
Analyses were performed using SAS version 9.1 (SAS Inc.,
Cary, NC), SPSS version 15.0 (SPSS Inc., Chicago, IL), and
LMSChartmaker.26A value of p ? 0.05 was considered signifi-
cant for all tests, and FDR ? 0.05 was used to correct results for
growth chart comparison.
Neurology 79October 16, 2012
RESULTS Of 878 female participants, 8 RNHS and
54 supplemental participants were excluded because
of unconfirmed diagnoses. The remaining partici-
pants, 726 with classic RTT and 90 with atypical
RTT, were followed up to 3.25 years (mean 1.5
Demographics. Participants were mostly Caucasian
and non-Hispanic (table 2). Birth year ranged from
1945 to 2008. Nearly all lived at home, and none
born after 1997 lived in a group home or institution.
Two-thirds were diagnosed before age 4 years, and
half were enrolled by age 10.
Mutation frequencies. Among 816 participants, 751
(92%) had mutations in MECP2, including 689
with classic RTT (95%) and 62 with atypical RTT
(69%). The 8 common point mutations made up
56% of classic RTT and 37% of atypical RTT muta-
tions (table 1).
Measurements. Overall, 9,749 observations were re-
corded, averaging 12 per individual: 9,240 weight,
6,992 height, 6,178 FOC, and 6,937 BMI; the major-
number of observations decreased with age but re-
mained greater than 40 per year in classic RTT (table
e-1). Height measurements included 44% recumbent,
surements. After 3 years of age, the majority were mea-
sured standing. Measurement type did not affect
average height before 5.5 years, beyond which average
height or length was shorter in participants measured
recumbent. After 2.5 years, CSS was higher for partici-
pants measured recumbent.
Summary statistics. Birth. Mean birth measurements
in participants with both classic and atypical RTT
were similar to those in the normative population
(data not shown).
Adulthood. Adult RTT measurements were homo-
geneously distributed from normal (obese in the
cases of weight and BMI) to extremely low (table 3).
Average adult age was 25.4 years. Final adult height,
weight, BMI, and FOC for participants with classic
and atypical RTT were lower than those for non-
RTT participants (p ? 0.001); however, no differ-
ence existed between those with classic and atypical
Growth references. The LMS method generated clas-
sic RTT charts with empirical data evenly distributed
at younger ages and moderately dense at older ages.
At ?3 SD the charts tended to overestimate weight
Table 1MECP2 mutation categories and frequencies
(n ? 726)
(n ? 90)
Type or location
Truncating (pre-C-terminal) 405.55 5.6
C-terminal truncating 51 7.01213.3
Large deletion577.93 3.3
Other missense75 10.36 6.7
T158M80 11.02 2.2
R294X41 5.74 4.5
R270X42 5.82 2.2
R133C 314.3 1011.1
No mutation37 5.1 2831.1
Table 2Demographic characteristics of the
cohort (n ? 816)a
% all with
Gestational age range 27?36 wk
Year of birth
Born before January 1, 1997
Age at enrollment
Age of diagnosis
aData could not be collected on all participants for all de-
Neurology 79October 16, 2012
by 0.2?2 kg near 5 years and height by 0.2?1.8 cm
near 10 years. Empirical fit for FOC was consistent
Patterns of growth in classic RTT. Weight. The mean
weight trajectory for classic RTT diverged below the
normative pattern at age 6 months (figure 1). Mean
weight was lower than the normative at 13 months
(p ? 0.04, FDR ? 0.05). By age 12.5 years, mean
weight was equal to the normative second percentile.
Weight distribution was wider than that in unaf-
fected children, and between 7 and 12 years, 6.4%
were above the 98th percentile. By 18 years, 71% of
participants were below the second percentile on the
normative reference. When participants were exam-
ined individually, 80% fell below the second percen-
tile for weight at some point during development;
only 51% of participants declined in weight velocity
Height. Mean RTT height fell below the norma-
tive mean by 17 months (p ? 0.02, FDR ? 0.03)
(figure 1). By age 12 years, mean height was ?2 SD.
The distribution of height was also wide; between 12
and 17 years, 7.9% of participants were taller than
the 98th percentile. By 18 years, 84.5% of adults
were below the second percentile for height. Individ-
ual height velocity fell ?1.3 SD in 41% of partici-
pants, and 87.5% were below the second percentile
for height at some point.
FOC. Mean FOC for RTT fell below the norma-
tive mean by 1 month (p ? 0.0001, FDR ? 0.0001)
(figure 2). By 2 years, mean FOC was ?2 SD; no
individual had an FOC above the 98th percentile
thereafter. At 18 years, 81% were below the second
percentile. Individual FOC velocity fell ?1.3 SD in
44%, and 86% had a minimum FOC below the sec-
ond percentile at some point.
BMI. The mean BMI trajectory for children with
RTT fell slightly below that for normal children at
4?5 months, but mean RTT BMI was similar to the
normative mean after 9 months (figure 2). At 18
years, the average BMI was 20, compared with 21 for
normal women. The distribution was wide with 36%
below the normative second percentile and 19% above
the 98th percentile at some point in development, typi-
cally between 12 and 17 years. Despite normal average
fell ?1.3 SD in 57% of participants.
Growth patterns. When proportions of measure-
ments were compared, 5 distinct patterns emerged:
1) severe somatic growth deficit with microcephaly
(n ? 239); 2) preserved, normal somatic growth with
microcephaly (n ? 219); 3) moderate somatic
growth deficit with microcephaly (n ? 140); 4)
moderate somatic growth deficit with preserved, nor-
mal head size (n ? 21); and 5) normal growth (n ?
Classic vs atypical RTT. No differences in average
measurements were found between participants with
classic and atypical RTT. Growth patterns were dif-
ferent (p ? 0.01), with a higher proportion of partic-
ipants with atypical RTT exhibiting either preserved
somatic growth with microcephaly or normal growth
(patterns 2 and 5) (figure e-1A).
Based on secular trends. Mean standardized weight
was lower in participants born before 1997 (M ?
?1.86), compared with those born during or after
1997 (M ? ?1.42, p ? 0.05). A higher proportion
of participants born during or after 1997 exhibited
growth pattern 2, preserved somatic growth with mi-
crocephaly (p ? 0.001) (figure e-1B).
Rett syndrome characteristics. Functional limitations,
including overall severity, hand use, ambulation,
nonverbal communication, scoliosis, seizures, stereo-
typies, hyperventilation, sitting, and regression were
associated with lower adult measurements (table
e-2), but verbal language was not. Growth propor-
tions were associated with overall disease severity,
Table 3Average and extreme weight, height, FOC, and BMI values in adult women (>18 years) with
FOC, cm 21151.2
Weight, kg 2647.0
FOC, cm 2151.5
Abbreviations: BMI ? body mass index; FOC ? fronto-occipital head circumference.
Neurology 79October 16, 2012
hand use, ambulation, scoliosis, seizures, sitting (p ?
0.001) but not with language, stereotypies, hyper-
ventilation, or regression. Preserved somatic growth,
with or without microcephaly, was associated with
better outcome (patterns 2 and 5) (figure e-1, C–H).
Genotype and growth. Two- to 7-year age range and
mutation (n ? 494). Weight was higher in participants
with C-terminal truncation than in those with pre-
C-terminal truncation, large deletion, no mutation,
T158M, R168X, and R255X (p ? 0.001). BMI was
also higher in those with late truncation than in those
with either early truncation or large deletion (p ?
0.001). Head circumference was higher in those with
the R294X point mutation than in those with
R255X and R270X point mutations (p ? 0.001).
Seven- to 12-year age range and mutation (n ? 272).
Head circumference was smaller in participants
with pre-C-terminal truncation than in the other
missense and no mutation groups, and smaller in
those with large deletion than in those with no
mutation (p ? 0.05).
Adult (n ? 169). No significant difference in final
average adult measurements existed among mutation
Figure 1Height and weight in unaffected children (orange) and children with classic Rett syndrome (blue)
Height in Rett syndrome falls below the normative population at 21 months, and weight is lower at 13 months. Pubertal
growth spurt is attenuated.
Neurology 79 October 16, 2012
Growth velocity and mutation. The decline in stan-
dardized weight from baseline to 6 years was lower
in participants with C-terminal truncation than in
those with pre-C-terminal truncation, large dele-
tion, other missense, T158M, R255X, and R270X
(p ? 0.001). Average weight velocity was lower for
those with R270X than for those with R306C and
R133C (p ? 0.001). BMI velocity was higher in
those with C-terminal truncation than in those
with large deletion, other missense, R294X, and
R270X (p ? 0.001). Head circumference velocity
was lower in those with pre-C-terminal truncation
than in the C-terminal truncation group (p ?
Age at minimum SD score and mutation. Participants
with pre-C-terminal truncation and large deletion
reached their minimum standardized weight at an
earlier age than those with C-terminal truncation
(p ? 0.05). Likewise, those with pre-C-terminal
truncation reached their minimum BMI before those
with C-terminal truncation (p ? 0.05). The pre-C-
terminal truncation group reached minimum FOC
before the other missense group, and those with
R270X reached their FOC nadir before those with
Figure 2 Head circumference and body mass index (BMI) in unaffected children (orange) and children with
classic Rett syndrome (blue)
Head circumference in Rett syndrome falls below the normative population at 1 month of age. Average BMI is similar to
normative population, but distribution is wider.
Neurology 79October 16, 2012
R294X and R133C (p ? 0.05). None of these asso-
ciations was influenced by age of the participants at
the final measurement.
Puberty and growth in classic RTT. Age of pubertal
onset (n ? 66) ranged from 5.1 to 16.6 years and was
associated with final height, weight, and BMI (p ?
0.001) but not with any measures of disease severity
or specific MECP2 mutations. Normal pubertal on-
set adjusted for race occurred in 85%, with preco-
cious puberty in 12% and late-onset puberty in 3%.
Patterns of growth varied with age of pubertal onset
(p ? 0.001). Average age of pubertal onset was
8.8 ? 0.9 years in participants with normal growth
(pattern 5), 9.3 ? 1.7 years in those with microceph-
aly and preserved somatic growth (pattern 2), 10.2 ?
0.8 years in those with microcephaly and mild
somatic growth failure (pattern 3), and 11.5 ? 1.7
years in those with microcephaly and global somatic
growth failure (pattern 1) (figure e-1I).
DISCUSSION Growth studies in RTT have been
limited to small populations1,27–29or specific anthro-
pometric measurements,30,31and most were per-
formed before MECP2 mutations were discovered or
used statistical methods insufficient for calculating z
scores. This study demonstrates that the patterns of
growth in RTT are different from those in unaffected
individuals. Functional gross motor, fine motor, and
nonverbal language deficits, as well as the presence of
seizures, scoliosis, and RTT behaviors earlier in life
are associated with severity of growth failure in late
childhood and adolescence. Research on acquired
microcephaly suggests that sparing of somatic growth
confers a better developmental outcome.32We found
that despite persistent microcephaly, preserved so-
matic growth occurs in 45% of girls with RTT and is
associated with better development and lower sei-
zure, scoliosis, and RTT behavior burden, contra-
dicting dogma that “proportional” microcephaly
conveys a protective effect. The resting metabolic
rate is higher in patients with RTT than in those
with other developmental disabilities,33and intensive
nutritional therapy improves growth outcomes.
These findings suggest both that growth is an impor-
tant outcome for clinical trials and that improved
nutrition could moderate the association between
growth and development.34
No study has adequately examined BMI in RTT.
One assessed BMI in large age clusters that precluded
analysis of BMI velocity.35Despite height and weight
failure, mean BMI in classic RTT is similar to that of
unaffected, healthy females. Because BMI distribu-
tion in RTT is wide, standard BMI values overesti-
mate low BMI. Conversely, decreasing BMI velocity
was a sensitive marker for weight failure when abso-
lute values were normal. Notably, the normal puber-
tal increase in height or weight velocity was absent in
RTT. Although height in normative references is in-
variably positively skewed, height in adults with
RTT was negatively skewed, suggesting that few
women with RTT are tall, whereas many are ex-
Mutation in MECP2 was associated with growth
velocity, the crucial prerequisite of growth failure.
Growth failure was more evident in those with muta-
tions associated with greater clinical severity such as
pre-C-terminal truncation and R270X than in muta-
tions associated with a milder burden such as
R306C, R133C, and C-terminal truncation.17Con-
ditional references based on genotype could aid in
studying the factors contributing to growth failure in
RTT and response to treatment.
Concern exists that disease-specific charts based
on biased methodology or insubstantial data will
become standards for a disorder.36However, most
individuals with RTT after age 7?8 years have mea-
surements less than ?3 SD compared with those for
unaffected individuals.30,35Statistical comparisons
beyond ?3 SD contain insufficient empirical data
and are imprecise.37This study addressed methodo-
logic concerns by recruiting 7% of the RTT popula-
tion in the United States, ranging in disease severity
and coming from many racial, ethnic, and geograph-
ical backgrounds, through the International Rett
Syndrome Foundation. Although not designed for
longitudinal data, LMS produces precise curves38and
was selected from among 30 methods by the World
The benefit of the World Health Organization
prescriptive standards based on normal, healthy,
breastfed international populations remains un-
clear.40Alternately, empirical data restricted to cer-
tain outcomes regarded as favorable could represent
the standard for growth in the disorder. One limita-
tion of this study is that quantitative measures of
therapeutic or nutritional intervention were not in-
corporated. Gastrostomy tube supplementation af-
fects growth, and other interventions such as physical
therapy may as well. Several potential contributors to
growth failure, such as nutrition, seizure disorder,
anxiety, constipation, gastroesophageal reflux, and
orthopedic issues, can be modified. The RNHS
study is currently collecting information on these as-
pects of health care that will be included in subse-
quent analyses designed to identify prescriptive
targets for normal growth.
Our growth charts will allow researchers to more
precisely examine the effects of novel RTT treat-
ments. Moreover, clinicians will be able to assess
medical health and the effect of interventions. As
Neurology 79October 16, 2012
definitions of “healthy” individuals with RTT
emerge from the natural history study, prescriptive
standards of growth will provide objective data about
how individual children with RTT should be grow-
ing. Comparison of aggressive and standard treat-
ment of variables influencing growth could lend
further insight into the interplay between nutrition,
growth, and health in individuals with RTT.
Daniel C. Tarquinio: study conduct, data collection, manuscript prepara-
tion. Kathleen J. Motil: study conceptualization, study conduct, data col-
lection, manuscript review. Wei Hou: statistical analysis, manuscript
review. Hye-Seung Lee: study conduct, data collation and statistical anal-
ysis, manuscript review. Daniel G. Glaze: study conduct, data collection,
manuscript review. Steven A. Skinner: study conduct, data collection,
manuscript review. Jeffrey L. Neul: study conduct, data collection, manu-
script review. Fran Annese: study conduct, data collection, manuscript
review. Lauren McNair: study conduct, data collection, manuscript re-
view. Judy O. Barrish: study conduct, data collection, manuscript review.
Suzanne Geerts: study conduct, data collection, manuscript review. Jane
B. Lane: study conceptualization, study conduct, data collection, manu-
script preparation. Alan K. Percy: Study conceptualization, study con-
duct, data collection, manuscript preparation.
The authors thank Professor Tim Cole for his advice on growth reference
D. Tarquinio reports no disclosures. K. Motil serves on the International
Rett Syndrome Foundation (IRSF) Scientific Review Committee and is
funded by the NIH. W. Hou and H.-S. Lee report no disclosures. D.
Glaze serves on the Scientific Advisory Board of IRSF and the Executive
Committee of RettSearch and is funded by the NIH. S. Skinner serves on
the Scientific Advisory Board of IRSF and is funded by the NIH. J. Neul
serves on the Scientific Advisory Board of IRSF and the Executive Com-
mittee of RettSearch and is funded by the NIH. F. Annese is funded by
the NIH. L. McNair is funded by the NIH. J. Barrish serves on the IRSF
Professional Advisory Board and is funded by the NIH. S. Geerts is
funded by the NIH. J. Lane is a paid consultant of the IRSF regarding
clinical matters related to Rett syndrome and is funded by the NIH. A.
Percy serves on the Scientific Advisory Board of IRSF is the principal
investigator for the Rare Diseases Clinical Research Center grant for An-
gelman, Rett, and Prader-Willi syndrome grant (NICHD); is funded by
the NIH; and receives administrative support from the UAB Civitan In-
ternational Research Center. Go to Neurology.org for full disclosures.
Received December 8, 2011. Accepted in final form May 29, 2012.
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Neurology 79 October 16, 2012
DOI 10.1212/WNL.0b013e31826e9a70 Download full-text
; Published online before print October 3, 2012; 2012;79;1653
Daniel Charles Tarquinio, Kathleen J. Motil, Wei Hou, et al.
Growth failure and outcome in Rett syndrome : Specific growth references
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