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Repetitive Behavior in Rubinstein–Taybi Syndrome: Parallels with Autism Spectrum Phenomenology

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Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS.
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Repetitive behaviour in Rubinstein-
Taybi syndrome: Parallels with autism
spectrum phenomenology
Jane Waite, Joanna Moss, Sarah Beck, Caroline Richards, Lisa Nelson,
Kate Arron, Cheryl Burbidge, Katy Berg and Chris Oliver
Cerebra Centre for Neurodevelopmental Disorders,
School of Psychology,
University of Birmingham
Please use this reference when citing this work:
Waite, J., Moss, J., Beck, S. R., Richards, C., Nelson, L., Arron, K., Burbidge, C., Berg, K., &
Oliver, C. (2015). Repetitive behaviour in Rubinstein-Taybi syndrome: Parallels with autism
spectrum phenomenology. Journal of Autism and Development Disorders, 45, 1238-1253.
The Cerebra Centre for Neurodevelopmental Disorders,
School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT
Website: www.cndd.Bham.ac.uk E-mail: cndd-enquiries@contacts.bham.ac.uk
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Abstract
Background. Syndrome specific repetitive behavior profiles have been described previously.
A detailed profile is absent for Rubinstein-Taybi syndrome (RTS).
Method. The Repetitive Behaviour Questionnaire and Social Communication Questionnaire
(SCQ) were completed for children and adults RTS (N = 87), Fragile-X (N = 196) and Down
(N = 132) syndromes, and individuals reaching cut-off for Autism Spectrum Disorder (ASD)
(N = 228).
Results. Total and matched group analyses were conducted. A phenotypic profile of
repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated
with social-communication deficits or degree of disability.
Conclusions. Repetitive behavior should be studied at a fine-grained level. A dissociation of
the triad of impairments might be evident in RTS.
Keywords: Rubinstein-Taybi syndrome, Autism Spectrum Disorder (ASD), Repetitive
behavior, ritualistic behavior,
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Repetitive Behavior in Rubinstein-Taybi Syndrome Parallels with Autism Spectrum
Phenomenology
Rubinstein-Taybi syndrome (RTS) occurs in approximately 100,000 - 125,000 live births and
is caused by breakpoints, mutations and microdeletions on chromosome 16p13.3 or by a
mutation in the E1A-binding protein (p300) or CREB-binding protein (CBP). Intellectual
disability ranges from mild to profound with moderate intellectual disability occurring most
commonly (Hennekam, 2006; Lacombe, Saura, Taine & Battin, 1992). It has been
hypothesised that impairments in RTS may be underpinned by long-term memory deficits
associated with mutations in the CREB binding protein (Alarcon et al., 2004; Wood et al.,
2005; Weeber & Sweatt, 2002). Diagnosis is usually by clinical features such as the
characteristic facial phenotype including broad nasal bridge, high arched eyebrows and
downwards slanting palpebral fissues. Other characteristics include growth deficiency,
microcephaly, broad thumbs and big toes (Hennekam, 2006; Udwin & Dennis, 1995).
Repetitive behavior has been noted as a phenotypic behavioral characteristic in RTS.
‘Repetitive behavior’ is an umbrella term encompassing a diverse range of behaviors
including adherence to routines, insistence on sameness, stereotyped behaviors and restricted
preferences (Turner, 1999). Repetitive behavior has traditionally been associated with
Autism Spectrum Disorder (ASD), because it forms one aspect of the triad of impairments
(World Health Organisation, 1993; American Psychiatric Association, 2013), and with a
greater degree of intellectual disability (Bartak & Rutter, 1976; Gabriels, Cuccaro, Hill, Ivers
& Goldson, 2005; Smith & VanHouren, 1996). In RTS, Stevens, Carey and Blackburn
(1990) found that over 50% of a sample of children (N=50) engaged in stereotyped motor
movements including hand stereotypy, spinning and rocking. Over 75% were reported to
insist on sameness. Recently, Galéra et al. (2009) reported higher rates of repetitive motor
movements in contrast to a heterogeneous intellectual disability group; however, because this
study did not contain syndrome specific comparison groups, conclusions cannot be drawn
about how these repetitive behaviors compare to behaviors observed in other syndromes. A
systematic cross syndrome approach to studying repetitive behavior in RTS is absent from the
literature.
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A systematic cross syndrome study of repetitive behavior in RTS could be conducted at a
broad or fine-grained level of description. Researchers who have studied repetitive behavior
in syndrome groups and neurodevelopmental disorders have focused on the severity or
frequency of repetitive behavior at a broad level, with behaviors grouped together and
described using composite scores (e.g. Lopez, Lincoln, Ozonoff & Lai, 2005). In contrast,
Turner (1997) examined repetitive behavior in ASD and noted that some subclasses of
repetitive behavior, such as stereotyped behavior, can be further divided into more specific
topographies, for example body, hand or object stereotypy. Turner proposed that, in order to
understand the aetiology of repetitive behavior, behaviour needs to be described at fine-
grained level as specific behaviours may have specific underpinnings.
Moss, Oliver, Arron, Burbidge and Berg (2009) used a fine-grained approach to study
repetitive behavior in seven neurodevelopmental disorders, not including RTS, and found
significant group differences, many of which were unrelated to degree of disability. These
findings suggest that a fine grained approach to studying repetitive behavior in other
syndromes might reveal phenotypic repetitive behavior profiles. For example, individuals
with Fragile-X syndrome (FXS) were more likely to engage in a greater number of
topographies of repetitive behavior in comparison to other syndrome groups and the majority
of these behaviors occurred more frequently than at least two groups. In contrast, individuals
with Prader-Willi syndrome showed a mixed profile and engaged in hoarding and adherence
to routine more frequently than at least two other groups. In addition, Moss et al. found
syndrome specific repetitive behaviors in Smith-Magenis (SMS) and Cri du Chat syndromes:
a strong preference for a particular people and attachment to specific objects respectively.
These findings concur with other studies of behavior in these syndromes (Cornish & Pigram,
1996; Haas-Givler, 1994; Wilde, Silva & Oliver, 2013).
Delineation of the repetitive behavior profile of RTS will have clinical utility and will inform
research, as has been demonstrated in other syndrome groups. For example, the observation
that a high proportion of individuals with Prader-Willi syndrome are likely to have strong
preferences for routines alerts clinicians to aspects of this syndrome that might contribute to a
person experiencing anxiety or negative emotions when routines are not followed (Woodcock,
Oliver & Humphreys, 2009a). Hence, greater understanding of repetitive behavior in RTS
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will aid clinical formulation by helping identify which repetitive behaviors might lead to
difficulties. Furthermore, a detailed description of the repetitive behavior in RTS will aid the
design of studies that focus on the aetiology of repetitive behavior in RTS. For example, an
executive dysfunction account of repetitive behavior has been proposed in ASD and there is
also growing evidence that executive dysfunction may underpin specific repetitive behaviors
in a number of genetic syndromes, neurodevelopmental disorders and psychiatric conditions
such as Obsessive Compulsive Disorder (Lawrence et al., 2006; Lopez et al., 2005; Lysaker,
Whitney & Davis., 2009; Turner, 1997; Woodcock, Oliver & Humphreys, 2009a, 2009b,
2009c; Yerys et al., 2009). Woodcock et al. (2009b, 2009c) for example, linked preference
for routine in Prader-Willi syndrome to difficulties with cognitive set-shifting.
This study describes the repetitive behavior profile of RTS at a fine-grained level and the
profile is compared to three other neurodevelopmental disorders in which repetitive behavior
has been described in detail: Fragile-X syndrome (FXS), Down syndrome (DS), and
individuals meeting the cut-off for ASD on an ASD Screening Tool: the Social
Communication Questionnaire (SCQ; Rutter, Bailey & Lord, 2003). This is the first time the
repetitive behavior profile of RTS has been described, and to our knowledge the first time that
the repetitive profiles of ASD and DS have been compared to other disorders at a fine-grained
level.
FXS, DS and ASD will act as a bench mark against which RTS can be contrasted.
Individuals meeting the cut-off for ASD on the SCQ are a suitable contrast group because
individuals with ASD engage in a higher intensity and frequency of repetitive behavior than
mental age matched comparison groups (Bodfish, Symons, Parker & Lewis, 2000; Hermelin
& O'Conner, 1963; Lord, 1995; Lord & Pickles, 1996; Richler, Bishop, Kleinke & Lord,
2007; Watt, Welnerby, Barber & Morgan, 2008). FXS are a suitable group because, similarly
to ASD, individuals engage in a wide range of repetitive behaviors and this syndrome is
genetically defined in comparison to the ASD cut-off group (Hatton et al., 2006; Moss et al.,
2009; Udwin & Dennis, 1995). Finally, DS are a suitable group as there is evidence that
individuals with DS engage in fewer repetitive behaviors than those with a codiagnosis of
ASD (Hepburn & MacLean, 2009; Moss, Richards, Nelson & Oliver, 2012). In particular,
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Moss et al. (2012) found that individuals with DS and ASD engaged in more stereotyped
behavior and repetitive speech than those without ASD.
Studying the repetitive behavior profile of RTS in contrast to individuals with ASD and FXS
has a further implication. As noted previously, repetitive behavior has been associated with a
greater degree of intellectual disability and autism spectrum phemenonology, which includes
social and communication deficits. There is debate about whether the triad of impairments in
ASD represent a unified deficit or whether the triad can be fractionated (Happe & Ronald,
2008). Individuals with RTS could present with a dissociation of ASD characteristics:
repetitive behavior without, or with fewer, social-communication impairments. This is
because people with RTS may have fewer social deficits than individuals with ASD as parents
often describe RTS children as friendly, particularly around adults (Goots & Liemohn, 1977;
Baxter & Beer, 1992; Stevens et al., 1990), and reports suggest a greater degree of sociability
in RTS relative to controls (Galéra et al., 2009; Nelson, 2010). While, social behavior is not
the main focus of this study, correlational analyses exploring the link between repetitive
behavior, social-communication deficits, and degree of disability will be conducted to explore
the factors associated with the repetitive behavior profile of RTS.
A direct comparison of these syndromes is difficult given the varying degrees of intellectual
and physical disability across groups. For example, FXS is characterised by mild-moderate
intellectual disability, RTS by moderate ID, and hearing difficulties are common in DS
(Udwin & Dennis, 1995). A greater degree of intellectual disability, poorer vision and poorer
hearing are known risk markers for repetitive behavior (Bachara & Phelan, 1980; McClintock,
Hall & Oliver, 2003; Murdoch, 1996; Smith & VanHouren, 1996; Tröster, Brambring &
Beelman, 1991). One way of managing demographic differences across groups is by matching
participants on these characteristics. However, this reduces the likelihood of each syndrome
sample representing their population. Therefore, both a total group (total sample) and
matching approach (matched sample) were adopted in this cross-sectional questionnaire
study. A matching approach was particularly useful for non-parametric data where differences
between the groups could not be controlled for statistically. In summary, the aims of this
study were to: 1) compare the profile of repetitive behaviors across RTS, ASD, DS and FXS,
2) explore the association between repetitive behavior and ASD phenomenology
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(communication and social interaction) across groups using the total sample, 3) to explore
associations between repetitive behavior and degree of disability across groups using the total
sample, and 4) to repeat aim one with matched participants to control for age, degree of
disability, verbal ability, and degree of mobility.
Methods
Recruitment
RTS. 202 primary caregivers of individuals with Rubinstein-Tabyi Syndrome were sent an
invitation letter and a counter-balanced questionnaire pack through the Rubinstein-Taybi
Syndrome UK Support Group. Questionnaires were sent to all families on the RTS UK
Support Group database. These families, along with the families recruited for the comparison
groups, were recruited as part of a large scale questionnaire study investigating cognitive and
behavioral difference in rare genetic syndromes and neurodevelopmental disorders (Arron,
Oliver, Berg, Moss & Burbidge, 2011; Berg, Arron, Burbidge, Moss & Oliver, 2007;
Burbidge et al., 2010; Moss et al., 2009; Moss et al, 2008; Oliver, Berg, Burbidge, Arron &
Moss, 2011). As the participants were recruited as part of an ongoing study investigating
cognitive and behavioral difference across a wide range of syndrome groups, nine other
syndromes and six other questionnaire measures were excluded from the analyses reported
here. Moss et al. (2009) has previously published the data depicting the repetitive behavior
profiles for six of these excluded groups and for the FXS group whose data was reanalysed as
a comparison group in the current study.
Comparison Group Recruitment. 500 families of individuals with Down syndrome were
invited through the Down Syndrome Association, 432 families of individuals with Fragile-X
syndrome were invited through the Fragile-X Society, and 1467 families of individuals who
were suspected as meeting diagnostic criteria for ASD were invited through eight branches of
the National Autistic Society in the London and West Midlands area.
Participants
Overall, 735 participants (28.26%) returned a questionnaire pack. The questionnaire packs
were then screened and exclusion criteria applied. Participants were excluded if they did not:
confirm on a demographic/background questionnaire that their child had a diagnosis from a
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professional of RTS, FXS, DS, or ASD (N = 41); had an additional chromosomal disorder (N
= 1); complete over 75% of the questionnaire pack (N = 8); have a child over four years of
age (the SCQ was inappropriate for children younger than four) or did not confirm their
child’s age (N = 19). In addition to the above criteria, SCQ scores on the SCQ were
examined for participants recruited via the National Autistic Society to ensure individuals in
the ASD group reached cut-off for an ASD diagnosis on this screening tool (SCQ; Rutter,
Bailey & Lord, 2003). The latter inclusion criterion was applied to ensure the ASD cut-off
group displayed the behavioral characteristics associated with ASD as it was not possible to
confirm diagnosis through clinical assessment due to the large sample size and the use of
questionnaire methodology. A further twenty-three individuals were excluded because they
did not meet the cut-off.
The demographic characteristics of the remaining participants (N = 643) are displayed in table
1 (left hand side). Of these remaining participants 57.5% were diagnosed by a paediatrician,
25.43% by a clinical geneticist, 4.53% by a GP, 4.73% by a psychiatrist, 2.15% by a clinical
psychologist, 1.45% by an educational psychologist and 4.2% by another professional.
Insert table 1 about here
Measures
Demographic Questionnaire. The demographic information of the person with a genetic
syndrome was collected using the background questionnaire. This included information on
age, gender, mobility, verbal ability (more than 30 words/signs), primary/secondary diagnosis
of a genetic syndrome, and when and by whom the diagnosis was made.
Wessex Scale (Kushlick, Blunden & Cox, 1973). The Wessex Scale is a short informant rating
scale of degree of disability. The items evaluate the social and physical attributes of the
individual forming five subscales: self help, continence, mobility, speech and literacy. The
measure has modest reliability but it has been as noted to be an effective tool for large scale
questionnaire studies (Palmer & Jenkins, 1982).
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Repetitive Behavior Questionnaire (RBQ; Moss et al., 2009). The RBQ is a 19 item informant
questionnaire that measures discrete, observable repetitive behaviors. Each repetitive behavior
is operationally defined and examples of each behavior are provided. Repetitive behaviors
form a total score and five scaled subscales: stereotyped behavior, restricted preferences,
insistence on sameness, compulsive behavior and repetitive speech. The frequency of the
behaviors is scored on a five-point likert scale. Participants engaging in a repetitive behavior
once or more than once a day (scoring 3 or 4 on an item) are deemed to be scoring above the
clinical cut-off for that behavior. For brevity and
to avoid repetition the clinical-cut off scores and analyses of these scores are not included in
this paper; however, they can be obtained at [insert link to electronic supplementary file 1].
Moss et al. (2009) found that the RBQ has good inter-rater reliability, good test-retest
reliability at item level, and good concurrent and content validity with the repetitive behavior
subscale of the Autism Screening Questionnaire (Berument, Rutter, Lord, Pickles & Bailey,
1999).
Social Communication Questionnaire: Lifetime Version (SCQ; Rutter et al., 2003; previously
the Autism Screening Questionnaire
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(ASQ); Berument et al., 1999). The SCQ is a 40 item
informant screening questionnaire for the presence of Autism Spectrum Disorder in people
with intellectual disabilities. A total score and three subscales can be calculated:
communication, repetitive and stereotyped patterns of behavior, and social interaction.
Individuals who score 15 or above on the SCQ meet the screening cutoff for ASD. Berument
et al. (1999) validated the SCQ with 200 children sampled from developmental disorder
clinics (sensitivity = 0.85; specificity = 0.75). The total score on the SCQ relates strongly to
total score on the Autism Diagnostic Interview - Revised even after age, gender, language
ability and performance IQ were taken into account (Lord, Rutter & Couteur, 1994), which
suggests the measure has high concurrent validity (Berument et al., 1999).
In the current study a proportional communication subscale was used for the SCQ (Moss,
Oliver, Nelson, Richards & Hall, 2013) because the number of nonverbal participants varied
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The Autism Screening Questionnaire (ASQ) was used in the FXS group while the SCQ was used for the other
groups. Item 20 (social chat) differed between the versions for nonverbal participants so to ensure consistency
this item was treated as missing data and prorated for nonverbal participants by computing the mean score for
other completed items within the communication subscale. The use of the prorated item did not alter the
significance or direction of results.
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across the groups. Nonverbal participants cannot score on all items in the standard
communication subscale so the proportional subscale avoids group means being artificially
lowered. This was calculated by applying a formula to the communication subscale for
nonverbal participants (proportional formula = score on communication subscale / 8 x 13).
Data analysis
Total and Matched Groups Analyses. To maximise the sample size and the likelihood of each
sample
representing their given population the majority of analyses was conducted with the total
sample (N = 643). In addition, to control for the impact of particular demographic variables, a
subset of the total sample formed a matched sample (N = 168). The sample was matched for
verbal ability (speech score on the Wessex), self-help score, and age. Self-help score was
employed as an indicator of degree of disability. Participants were also matched for mobility,
although this was only partially successful due to the severity of mobility problems in FXS.
The groups were not matched for vision and hearing because it was not possible to match a
sufficient number of participants if these variables were taken into account. The demographic
characteristics for the matched group are displayed in table 1 (right hand side).
Data analysis strategy. Data obtained from the Repetitive Behavior Questionnaire at subscale
and item level violated the assumption of normality (Kolmogorov-Smirnov: p < .05). These
data could not be transformed so non-parametric analyses of variance were used. The groups
were compared at full scale, subscale and item level of the RBQ using Kruskall-Wallis non-
parametric analyses of variance and pairwise Mann-Whitney U tests. The RBQ has item level
reliability so analyses were carried out for all items for all groups, irrespective of group
differences at subscale level. The above analyses were conducted for the total sample and also
for the matched sample of participants (matched for age, self-help score and verbal ability
across groups).
In addition, for the total sample, Pearson partial correlations were conducted to examine
associations between scores on the subscales of the RBQ and the social interaction and
communication subscales of the SCQ while controlling for a proxy measure of intellectual
disability (self help score from the Wessex Scale). The repetitive and restricted behavior
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subscale of the SCQ were not compared to the RBQ due to overlap of items. Pearson partial
correlations were deemed appropriate for subscale analyses even though some subscales were
non-Gaussian because of a moderate sample size and the absence of skewness greater than
2.0 (Motulsky, 1995; Kendall & Stuart, 1958). The partial correlations would have been less
robust at item level. Finally, Spearman Rho correlations were conducted to explore the
association between repetitive behavior and intellectual disability (self help score of the
Wessex Questionnaire). This analysis was carried out at item level so that the possible
association with intellectual disability could be discussed in relation to the item level analysis
of the repetitive behavior profiles. Spearman Rho correlations were conducted as opposed to
Pearson correlations because at item level several variables were skewed above 2.0, and
several over 4.0. These analyses were exploratory so a conservative alpha level of .005 was
used throughout in order to minimise the chances of type II error.
Results
Subscale Level Analyses. Analyses were conducted to compare the total and matched
samples’ scores on subscales and items of the Repetitive Behavior Questionnaire. The results
of these analyses for the total and matched groups are displayed in table 2 (left and right side
respectively). The total and matched analyses revealed a significant main effect of group for
all the subscales and for the verbal and nonverbal full-scale scores (ps <.005).
Insert table 2 about here
In the total and matched group analyses RTS had significantly higher scores than DS on the
stereotyped behavior, compulsive behavior, and verbal full scale subscales; however they did
not differ from the ASD or FXS groups. In the total group, the RTS and ASD groups fell
between the DS and FXS groups on the repetitive speech subscale with significantly higher
scores than the DS group but lower scores than the FXS group. This result differed slightly in
the matched group because RTS had a significantly lower score than FXS on the repetitive
speech subscale, but did not differ from ASD or DS. The RTS group did not differ from any
group on the restricted preferences and insistence on sameness subscales in either the matched
or total analyses, although the ASD and FXS groups scored more highly on these subscales
than the DS group.
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Item Level Analysis. In the total group analyses, there were significant differences for 16 out
of 19 items (p <.005). Significant differences were absent for tidying up, organising objects,
and spotless behavior. The results of the post hoc analyses for the total sample are displayed
in figure 1 in the format devised by Moss et al. (2009). In this figure a plus sign indicates that
the group is scoring significantly higher than another group on an item, whereas a minus sign
indicates that the group is scoring significantly lower than another group on that item.
Insert Figure 1 about here
Visual inspection of figure 1 reveals that people with RTS had the most varied profile of
repetitive behavior in comparison to DS who had lower levels of repetitive behavior, and
ASD and FXS who had heightened levels of repetitive behavior across a wide range of
behaviors. RTS had heightened levels of stereotypy, hoarding, restricted conversation,
preference to routine, repetitive questions and phrases in comparison to DS. However, RTS
had lower levels of restricted conversation, repetitive phrase and echolalia than ASD and
FXS, lower levels of adherence to routine and hand stereotypy than FXS, and lower levels of
cleaning than ASD. When the analyses were repeated with the matched sample, significant
group differences remained for body and hand stereotypy, restricted conversation, preference
for routine, repetitive questions, repetitive phrase, and echolalia. These analyses are displayed
in table 3. In agreement with the total group analyses RTS had heightened scores on body
stereotypy relative to DS, which did not differ from scores for ASD or FXS. RTS had lower
levels of restricted conversation and repetitive phrases relative to ASD and FXS. However,
RTS were no longer significantly different from DS for repetitive questions but the group did
not differ from FXS either. There was a significant difference between FXS and DS indicating
that the scores for RTS were between these two groups.
Insert table 3 about here
Association with Autism Spectrum Phenomenology. The association between repetitive
behavior and social-communication deficits for the total group are displayed in table 4.
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Insert Table 4 here
In RTS, there were no significant associations between the repetitive behavior measured by
the RBQ and social-communication deficits measured by the SCQ. There are associations
between repetitive behavior and social-communication deficits in ASD, DS and FXS (ps <
.005). In ASD greater social-communication deficits were associated with compulsive
behavior, insistence on sameness and total nonverbal score. Social interaction deficits were
associated with compulsive behavior and total score. In FXS social-communication deficits
were associated with repetitive language, whereas social interaction deficits were associated
with compulsive behavior, insistence on sameness and total nonverbal score. In DS social-
communication deficits were associated with stereotypy, repetitive language and total
nonverbal score, and social interaction deficits were associated with stereotyped behavior and
total nonverbal score.
Ability Level and Repetitive Behavior. Spearman Rho correlations exploring the association
between degree of disability (measured by the Wessex Self Help Score) and items from the
RBQ are displayed in Table 5. The fewest significant correlations between repetitive
behavior and self-help score were for the RTS group. Intellectual disability was associated
with object
stereotypy and echolalia.
Insert Table 5about here
In people with ASD, ability level was associated with all topographies of stereotypy, rituals,
lining up and attachment to objects, repetitive phrases and echolalia. In DS object stereotypy,
body stereotypy, and attachment to objects, repetitive phrase and echolalia were related to
ability level. A similar pattern was observed in FXS whereby all topographies of stereotypy,
all repetitive speech items, and attachment to people were related to ability level.
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Discussion
Previous research has found that specific repetitive behavior profiles can be described for a
range of neurodevelopmental disorders, lending support for studying repetitive behavior at a
fine-grained level of description (Turner, 1997; Moss et al., 2009). In addition, repetitive
behavior has been linked to social-communication deficits, associated with ASD, and ability
level (World Health Organisation, 1993; American Psychiatric Association, 1994;
McClintock et al., 2003). In this paper we described the repetitive behavior profile of RTS in
relation to ASD, DS and FXS. This was the first time the repetitive behavior profile of RTS
has been described, and to our knowledge the first time that the repetitive profiles of ASD and
DS have been compared to other disorders at a fine-grained level. In addition we examined
how the repetitive behavior profile relates to ASD phenomenology and ability level. This was
conducted at a total group level and at a matched group level.
A descriptive summary of the key findings is displayed in table 6.
Insert table 6 about here
Analyses were conducted initially with the total sample. The RTS total group had an uneven
profile of repetitive behavior, engaging in a wide range of behaviors at a higher rate than DS
and at a similar level observed in ASD, for example, heightened repetitive questions. The
profile was consistent with that reported in previous literature on RTS that has highlighted
body stereotypy and adherence to routines as phenotypic behaviors (Stevens et al., 1990).
However, other behaviors such as restricted conversation, repetitive phrase and echolalia were
less pronounced in RTS and did not differ significantly from DS. The pattern of results
observed in the total group for RTS lends further support to studying repetitive behaviors at a
fine grained level of description. In particular, if repetitive vocalisations had been grouped
together it would have obscured this pattern in RTS.
The specificity of the RTS profile is of interest when considered in comparison to ASD, FXS
and DS generally. The DS group had lower repetitive behavior scores across the majority of
RBQ items, while ASD and FXS had heightened generalised scores across the majority of
items. Heightened generalised repetitive behavior in ASD is consistent with previous reports
of behavior in this disorder (Bodfish, Symons, Parker & Lewis, 2000; Hermelin & O'Conner,
1963; Lord, 1995; Lord & Pickles, 1996; Richler, Bishop, Kleinke & Lord, 2007; Watt,
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Welnerby, Barber & Morgan, 2008). However, even within the ASD and FXS profiles there
was evidence of specificity, for example, FXS engaged in more repetitive questioning than
any other group in all analyses conducted.
Matched group analyses were conducted to examine which of these results would remain
significant when age, intellectual disability and verbal ability were accounted for. A
proportion of the significant results were lost when the matched sample analyses were
conducted. Matching groups has the disadvantage of lowering sample size, thus, it is difficult
to be conclude whether changes occurred because the associations in the total group analyses
were driven primarily by the demographic variables, or whether they were lost because of less
power to detect group differences. However, the key benefit of the matched analyses in this
study is that it added validity to the positive results that remained significant.
These analyses revealed that the RTS group had comparable levels of body stereotypy to ASD
(significantly more than in DS). The RTS group engaged in restricted conversation and
repetitive phrase less frequently than both ASD and FXS, and although scores on the
repetitive questioning item were no longer significantly heightened in comparison to DS the
scores are not significantly lower than ASD and FXS either. Inspection of the mean score on
the repetitive behavior item reveals that RTS have a similar mean on this item to ASD. Taken
together these results continue to support the dissociation of repetitive behaviors within
groups, along with varying levels of repetitive behavior across groups.
We explored how repetitive behaviors related to social-communication deficits in RTS
relative to the comparison groups. Repetitive behavior in RTS was not associated with the
social-communication deficits measured by the SCQ. The absence of associations occurred
even though individuals with RTS scored highly on specific topographies of repetitive
behaviors, in line with scores obtained by the ASD group (body stereotypy, routine and
repetitive questions). This is an interesting result as repetitive behavior and socio-
communication deficits form the triad of impairments in ASD (World Health Organisation,
1993; American Psychiatric Association, 1994) , and the absence of an association fits with a
recent review of the literature that summarised evidence from twin studies and the ASD
literature to argue that different sets of genes may underpin the separate components of the
triad of impairments (Happe, 2008). It is important to note that an absence of an association
between repetitive behavior and socio-communicative deficits in RTS does not negate the
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possibility of a unified mechanism underpinning triad of impairments in ASD because these
findings do not prove that ASD cannot emerge from one genetic origin that codes for the
entire pathway. However, it does point towards the possibility that different genetic
components may give rise to different aspects of the triad of impairments. Furthermore,
because repetitive behaviors scores in ASD were found to mirror some scores in RTS and
FXS, it is possible that the mechanisms that underpin these repetitive behaviors are not
distinct to ASD.
It was surprising that the strongest relationships between social-communication deficits and
repetitive behavior were found for FXS and DS and not for the ASD group. However, this
pattern is likely to be a product of the sampling method used for the ASD group. The ASD
group were a more homogenous group because they were selected based on their behavioral
characteristics. Hence, in comparison to the ASD group, there may be more individuals
obtaining low scores on the RBQ and low scores on SCQ in the contrast groups, and this may
have given rise to stronger, more linear associations between these measures.
The finding that RTS has some highly specific heightened repetitive behaviors but that these
repetitive behaviors are not related to social-communication deficits suggests that this
syndrome might sit between disorders characterised by high repetitive behavior and social-
communication deficits (e.g. ASD & FXS) and disorders with low repetitive behavior and
fewer social-communication deficits (e.g. DS). The confirmation of anecdotal reports of
repetitive behavior in RTS and the finding that these behaviors do not relate to social-
communication deficits fits with the anecdotal reports that RTS might have fewer social
deficits in comparison to other disorders (Goots & Liemohn, 1977; Baxter & Beer, 1992;
Stevens et al., 1990). It is unclear why repetitive questioning may be heightened in RTS
relative to other repetitive vocalizations such as echolalia and phrases. As socio-
communicative deficits are not associated with repetitive behavior in RTS it may be that
repetitive questions may have utility in RTS in the social environment. For example, in RTS
repetitive questions may elicit caregiver attention or be related to memory difficulties that
have been pointed towards in this syndrome (Alarcon et al., 2004; Wood et al., 2005; Weeber
& Sweatt, 2002).
Finally, it was found that some repetitive behaviors, namely, stereotypy, repetitive
phrases/signing and echolalia may be partly related to degree of intellectual disability. This is
17
consistent with previous studies that have explored the impact of ability level (McClintock,
Hall & Oliver, 2003; Smith & VanHouren, 1996). However, it is worth noting these behaviors
are unlikely be related solely to ability level given the variation found in repetitive behavior in
the matched sample. For example, there were significant differences between the matched
samples for stereotypy. There is also some variation across syndrome groups in respect to the
degree to which repetitive behaviors correlate with ability level (only object stereotypy and
echolalia are related to ability level in RTS). Furthermore, a large number of repetitive
behaviors do not correlate with age or ability in any of the groups although they relationships
are in the anticipated direction.
There are a number of implications of these findings. One potential mechanism that might
underpin specific repetitive behavior in RTS and may warrant further investigation is an
executive functioning deficit. Turner (1997) found that adherence to routine in individuals
with ASD was related to difficulties shifting set on a rule based card game. Woodcock,
Oliver and Humphreys (2009a, 2009b, 2009c) conducted a series of studies with individuals
with Prader-Willi syndrome to demonstrate a link between set-shifting deficits and resistance
to change. They used a broad range of methodologies including a questionnaire study,
naturalistic observations, manipulating environmental contingencies and brain scanning to
demonstrate this link. There is also evidence that suggests repetitive behaviors emerge in
individuals with Alzheimer’s patients alongside executive function impairments (Cullen et al.
2005). Given that repetitive behavior profiles can be described at a fine-level of description
further investigation should explore how specific executive function deficits might map on to
these profiles (Turner, 1997).
Fine-grained description of repetitive behavior has implications for clinical practice.
Repetitive behavior profiles provide a description of what is generally ‘typical’ within a
syndrome group and may help highlight potential key areas of need for particular groups, such
as an importance of routine. Clinicians may be able to use this information to target
interventions towards particular repetitive behaviors, or to predict which behaviors may pose
a challenge for families over time. Some families may find it useful to know that a particular
behavior, such as repetitive questioning, is common in a genetic disorder. In addition, these
profiles may help clinicians differentiate between individuals who are displaying repetitive
behavior that is characteristic of a genetic disorder and behavior that is related to an
18
underlying mental health issue such as the presence of Obsessive Compulsive Disorder, or the
presence of a co-morbid neurodevelopmental disorder such as ASD.
The possibility of a potential dissociation of the triad of impairments should influence how
ASD phenomenology is studied in the future and more may be learnt about the underpinnings
the triad of impairments from cross syndrome comparisons. This conclusion would be
strengthened in RTS by an empirical investigation of the social motivation of individuals with
RTS syndrome relative to other syndrome groups. To date, extensive research is being
conducted into the cognitive underpinnings of the social phenotype of RTS (Powis, Apperly,
Waite & Oliver, personal communication; Nelson, 2010) and it is hoped that this research will
lend further support to these conclusions.
There are a number of limitations of this study. The first limitation relates to the low response
rate from families of individuals with ASD and DS. This might have occurred because
families of individuals with these neurodevelopmental disorders are more frequently invited
to participate in research studies. A further possibility is that the families that did respond
were those with fewer care-giving demands due to supporting individuals with less severe
difficulties. If this occurred it could have reduced the differences between FXS and ASD and
increased the chances of finding significantly less behavior in DS. This seems unlikely for
DS as the results presented in this paper concur with the previous reports of behavior in DS
(Hepburn & MacLean, 2009). In addition, it could be argued that the opposite pattern of
responding should be expected from families of individuals with ASD in that families with
the greatest need are more likely to be motivated to respond.
Additional limitations include relying on the self-help score from the Wessex scale to assess
intellectual functioning. The self-help score gives an estimate of adaptive behavior; however,
a measure of cognitive non-verbal intelligence may have yielded different associations.
Therefore, further studies using direct assessment of intellectual functioning are needed to
validate the current findings. In addition, direct assessment of intellectual functioning and
child characteristics such as repetitive behavior would help overcome potential bias that arises
when one informant reports on multiple aspects of behavior.
A final caveat is that while behavior appears to occur at a similar frequency in ASD and FXS
it may be that differences would emerge if severity of the behavior was measured or if the
19
scale on the RBQ was expanded to allow for more frequent behavior to be reported (i.e. more
than once a hour). Despite this there still appears to be a good range of scores on the RBQ,
which suggests that the measure is capturing important differences between the groups.
In conclusion, RTS has a varied profile of repetitive behavior and certain behaviors are
elevated in this group (e.g. repetitive questioning, body stereotypy). In RTS these repetitive
behaviors appear to be unrelated to social-communication, and ability level does not fully
explain the profile. This supports the possibility of differing underlying aetiology and
developmental trajectories for specific repetitive behaviors that is distinct from the aetiology
of other ASD phenomenology. It is too simplistic to argue that all repetitive behaviors
decrease with age or that the presence of a repetitive behavior guarantees another. These
findings converge with those of Moss et al. (2009) who demonstrated the heterogeneous
nature of repetitive behavior profiles and lend support to Turner (1997) who argued that
grouping behaviors together serves to mask subtle differences that need to be observed if the
underlying mechanisms of these behaviors are to be understood.
20
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25
Figure Caption Sheet
Figure. 1 The repetitive behavior profiles of ASD, FXS, RTS and DS at item level. A plus sign
indicates that the group had a significantly higher mean score on that item than another group,
whereas a minus sign indicates that the group had a significantly lower mean score than another group
on that item.
Note. 5 point likert scale: 0 = never, 1 = once a month, 2 = once a week, 3 = once a day, 4 = more than
once a day.
Note. Behaviors listed from top clockwise are as follows: object stereotypy, body stereotypy, hand
stereotypy, attachment to people, attachment to objects, restricted conversation, cleaning, tidying,
hoarding, organising objects, rituals, lining up objects, completing behavior, spotless behavior,
adherence to routine, just right behavior, repetitive questions, repetitive phrases/signs, echolalia.
26
Figure 1.
27
Repetitive behaviour in RTS
Table 1. Demographic characteristics of the total group and matched samples broken down by syndrome group
Matched Group Analysis
Syndrome group
Syndrome group
A
B
C
D
A
B
C
D
ASD
FXS
RTS
DS
Df
χ²/
Kruskal
Wallis*
p value
Post hoc
analyses
(<.005)
ASD
FXS
RTS
DS
χ²/
Kruskal
Wallis*
p value
Post hoc
analyses
(<.005)
Na
228
196
87
132
42
42
42
42
Ageb
Mean
12.01
17.48
19.98
23.91
3
103.52*
<.001
B,C,D>A
D>B
15.55
15.50
15.86
15.90
0.30*
.960
-
SD
5.78
8.93
11.45
12.61
8.26
7.02
7.06
7.47
Range
4.10-
45.84
6.30-
47.49
4.24-
59.41
4.37-
62.00
6.61
45.84
6.31-
34.06
6.60-
32.80
4.95-
34.63
Gender
% male
86.0
100f
54.0
43.2
3
180.83
<.001
B>A,> C,D
83.3
100
57.1
38.1
44.91
< .001
B>A,C,D
A>D
Abilityc
% able or
partly abled
89.9
90.8
77.0
93.1
3
16.03
.001
A,B,D>C
90.5
90.5
83.3
95.2
3.34
.342
-
Mobilityc
% mobilee
95.2
72.0
77.9
92.4
3
54.52
<.001
A,D>B,C
90.5
71.4
82.9
88.1
6.49
.090
-
Verbal ability c
%verbal
92.5
96.3
84.9
96.2
3
14.55
.002
B,D>C
90.5
95.2
88.1
97.6
3.59
.309
-
Hearingc
% normal
hearing
96.9
97.4
85.1
65.9
3
101.68
<.001
A,B>C>D
97.6
97.6
78.6
61.9
27.67
< .001
A,B>C,D
Visionc
% normal
vision
96.5
88.1
85.1
63.4
3
75.66
<.001
A>B,C>D
97.6
88.1
78.6
61.9
19.42
< .001
A> C, D
B>D
SCQ
Mean
SD
26.36
5.48
21.00
6.79
17.15
5.51
9.84
7.07
3
255.28
<.001
A>B>C>D
27.72
5.44
24.11
5.42
17.33
5.53
11.45
8.27
71.81
< .001
A > B > C >
D
Groups: ASD Autism Spectrum Disorder, FXS Fragile X Syndrome, RTS Rubinstein-Taybi Syndrome, DS Down Syndrome
a N may vary across analyses due to missing or incomplete data
b in years
c information obtained from the Wessex self help scale (Kushlick et al, 1973)
d Those scoring 6 or above on the self help subscale. Self help is derived from summing three items regarding independent feeding, washing and dressing. Items are scored between one and
three resulting in a total score ranging between three and nine.
e defined as scoring 6 on the Wessex mobility subscale
f due to the X linked nature of the disorder 100% of FXS participants were male.
Note. FXS data previously presented in Moss et al. (2009). FXS group contains five additional participants who were added to dataset.
28
Repetitive behaviour in RTS
Table 2.
Total Group Analyses. Mean score, standard deviation, statistical analyses and post hoc analyses at subscale and full scale level of the RBQ.
Total Group (N = 643)
df
χ²
p
value
Post hoc
analyses
Matched Group (N = 162)
_______________________________
χ²
p
value
Post
hoc
analyses
A
B
C
D
A
B
C
D
ASD
FRX
RTS
DS
ASD
FRX
RTS
DS
Mean
(SD)
Mean
(SD)
Stereotyped behavior
6.56
(4.14)
6.47
(4.10)
6.21
(4.27)
2.39
(3.63)
3
96.85
< .001
ABC>D
7.42
(4.21)
6.95
(4.17)
5.97
(4.20)
3.07
(3.98)
24.04
<.001
ABC>
D
Compulsive behavior
8.42
(7.73)
7.03
(6.93)
7.11
(6.48)
4.29
(6.22)
3
37.53
< .001
ABC>D
8.07
(6.70)
7.99
(7.25)
7.26
(6.48)
3.39
(4.95)
16.82
=.001
ABC>
D
Restricted
preferencesᵃ
5.23
(3.63)
5.51
(3.71)
4.57
(3.45)
2.76
(3.02)
3
50.88
< .001
AB>D
5.91
(3.67)
5.51
(3.71)
4.48
(3.20)
3.28
(3.29)
14.51
=.002
AB > D
Insistence on
sameness
3.96
(2.79)
4.3
(2.73)
3.46
(3.07)
2.29
(2.78)
3
43.85
< .001
AB>D
4.49
(2.78)
4.49
(2.67)
3.30
(3.23)
1.88
(2.63)
21.05
<.001
AB > D
Repetitive speech
5.96
(4.00)
7.14
(3.67)
4.67
(3.69)
2.03
(2.84)
3
121.68
< .001
B>AC>D
6.47
(4.49)
7.58
(3.21)
4.81
(3.45)
2.76
(2.72)
30.57
<.001
AB > D
B > C
Verbal total scoreᵃ
29.33
(17.00)
30.08
(15.50)
26.01
(15.56)
13.25
(14.46)
3
94.82
< .001
ABC>D
32.09
(15.91)
31.35
(14.52)
25.87
(15.09)
13.87
(13.87)
32.14
<.001
AB
C>D
Nonverbal total scoreᵇ
22.41
(13.64)
21.80
(12.72)
19.34
(11.82)
9.88
(11.51)
3
93.03
< .001
ABC > D
23.84
(12.80)
23.44
(13.17)
18.85
(12.14)
9.78
(10.47)
32.69
<.001
ABC>
D
ᵃ Analysis only includes participants who are verbal
ᵇ Score calculated using nonverbal items for all participants
Note. Mean scores reported. Median scores are uninformative with too many zeros
Note. A letter missing from the post hoc analyses column indicates that this group was not different from other groups.
Note. FXS data previously presented in Moss et al. (2009). FXS group contains five additional participants who were added to dataset.
29
Repetitive behaviour in RTS
Table 3 Matched Sample Analyses. Mean score, standard deviation, statistical analyses and post
hoc analyses at item level of the RBQ.
Group:
A
B
C
D
ASD
FXS
RTS
DS
χ²
p value
Post hoc
Stereotyped behavior
Q1 Object stereotypy
2.54
(1.67)
1.86
(1.72)
1.67
(1.78)
1.24
(1.72)
11.07
ns
Q2 Body Stereotypy
2.24
(1.78)
2.29
(1.72)
2.45
(1.88)
0.86
(1.54)
20.55
<.001
A B C > D
Q3 Hand stereotypy
2.64
(1.69)
2.81
(1.58)
1.86
(1.88)
0.98
(1.60)
25.85
<.001
A B > D
Compulsive behavior
Q4 Cleaning
0.64
(1.36)
0.62
(1.27)
.02
(.15)
0.28
(0.97)
10.55
ns
Q5 Tidying
0.81
(1.31)
0.88
(1.29)
1.05
(1.48)
.43
(1.13)
6.45
ns
Q6 Hoarding
0.88
(1.45)
0.79
(1.39)
1.21
(1.68)
.31
(.98)
9.61
ns
Q7 Organising objects
0.81
(1.38)
0.86
(1.44)
0.93
(1.49)
.60
(1.23)
1.12
ns
Q12 Rituals
1.26
(1.70)
0.81
(1.55)
0.86
(1.52)
.39
(1.07)
7.40
ns
Q16 Lining up objects
1.21
(1.65)
1.42
(1.70)
1.43
(1.70)
.78
(1.35)
4.26
ns
Q18 Completing behavior
1.60
(1.67)
1.60
(1.75)
1.36
(1.68)
.68
(1.39)
8.34
ns
Q19 Spotless behavior
0.86
(1.49)
1.02
(1.63)
.40
(1.04)
.27
(.90)
7.54
ns
Restricted preferences
Q8 Attachment to peopleᵃ
1.41
(1.73)
1.82
(1.63)
1.77
(1.56)
1.38
(1.57)
2.06
ns
Q10 Attachment to objects
1.73
(1.87)
1.51
(1.81)
1.48
(1.80)
1.19
(1.63)
2.20
ns
Q13 Restricted conversationᵃ
2.71
(1.61)
2.64
(1.60)
1.23
(1.65)
0.79
(1.42)
30.07
< .001
A B > C D
Insistence on sameness
Q15 Preference for routine
2.74
(1.62)
2.78
(1.59)
1.97
(1.80)
1.05
(1.56)
23.70
< .001
A B > D
Q17 Just right behavior
1.68
(1.66)
1.67
(1.56)
1.33
(1.76)
0.83
(1.39)
8.27
ns
Repetitive Speech
Q9 Repetitive questionsᵃ
2.44
(1.76)
3.27
(1.23)
2.61
(1.70)
1.87
(1.67)
12.33
= .006ᵇ
B > D
Q11 Repetitive
phrases/signing
2.02
(1.79)
2.43
(1.71)
0.58
(1.16)
0.24
(0.89)
48.09
< .001
A B > C D
Q14 Echolaliaᵃ
1.88
(1.74)
2.12
(1.62)
1.55
(1.80)
0.68
(1.32)
15.12
< .005
A B > D
ᵃ Analysis only includes participants who are verbal.
ᵇ Differences for the repetitive question item were approaching significance at .006. Due to the exploratory
nature of the analysis, post hoc analyses were performed.
30
Repetitive behaviour in RTS
Table 4
Pearson’s partial correlations between subscales of the RBQ and the communication and social
interaction subscales of the SCQ for total groups (ASD, FXS, RTS & DS). Exploring the
relationship between repetitive behavior and Autistic Phenomenology (controlling for self help
score)
Group
Subscales of the
Social
Communication
Questionnaire
(SCQ)
RBQ:
Stereotyped
Behavior
Subscale
RBQ:
Compulsive
Behavior
Subscale
RBQ:
Restricted
Preferences
Subscale
RBQ:
Insistence
on
Sameness
Subscale
RBQ:
Repetitive
Use of
Language
Subscale
RBQ Total
Nonverbal
Score
ASD
SCQ: Communication
Subscale
.16
.19**
.11
.20**
.17
.23***
SCQ: Social
Interaction Subscale
.11
.19**
.13
.17
.08
.21**
FXS
SCQ: Communication
Subscale
.14
.17
.13
.17
.25**
.21*
SCQ: Social
Interaction Subscale
.20*
.28***
.20
.32***
.21*
.33***
RTS
SCQ: Communication
Subscale
.14
-.02
.15
-.10
.27
.00
SCQ: Social
Interaction Subscale
.08
-.10
.17
-.05
-.05
.00
DS
SCQ: Communication
Subscale
.53***
.27*
.28*
.23
.34**
.42***
SCQ: Social
Interaction Subscale
.51***
.21
.14
.15
.16
.35***
*** Significant at < .001, ** significant at <.005, * significant at <.01
ᵃᵇᶜᵈᵉᶠᶢ = .001, .005, .007, .007, .005, .006, & .001 respectively
31
Repetitive behaviour in RTS
Table 5
Total Group Analyses. Spearman’s correlations between degree of intellectual
disability and repetitive behavior at item level of the RBQ.
Group
ASD
FXS
RTS
DS
Stereotyped behavior
Q1 Object stereotypy
-.37***
-.33***
-.35**
-.40***
Q2 Body Stereotypy
-.41***
-.38***
-.12
-.32***
Q3 Hand stereotypy
-41***
-.41***
-.26
-.23*
Compulsive behavior
Q4 Cleaning
.12
-.08
.13
.18
Q5 Tidying
-.09
-.06
-.10
-.02
Q6 Hoarding
-.03
-.02
.13
.08
Q7 Organising objects
-.12
-.05
-.01
.05
Q12 Rituals
-.22**ᵇ
-.14
-.00
-.08
Q16 Lining up objects
-.22**ᶜ
-.10
-.14
.01
Q18 Completing behavior
-.12
-.07
-.14
-.09
Q19 Spotless behavior
-.13
.09
-.02
.04
Restricted preferences
Q8 Attachment to peopleᵃ
-.08
-.25**
.16
-.08
Q10 Attachment to objects
-.24***
-.19*
-.02
-.28**
Q13 Restricted conversationᵃ
-.03
-.06
-.12
-.07
Insistence on sameness
Q15 Preference for routine
-.10
-.12
-.04
.10
Q17 Just right behavior
-.17
-.06
-.06
-.04
Repetitive Speech
Q9 Repetitive questions
-.13
-.23**
-.16
-.24*
Q 11 Repetitive phrases/signing
-.22**ᶠ
-.27***
-.14
-.31***
Q 14 Echolalia
-.31***
-.29***
-.36**
-.28**
*** Significant at <.001** Significant at <.005
* Significant at < .01
ᵃ ᵇ ᶜ ᵈ ᵉ ᶠ Significant at .008, .001, .001, .009, .008 . & .001 respectively
32
Repetitive behaviour in RTS
Table 6
Descriptive summary of the key findings for ASD, FXS, RTS & DS
Group
ASD
FXS
RTS
DS
Degree of repetitive behavior
High
High
Moderate
Low
Degree of social/communication deficit (SCQ Score)
High
High
Moderate
Low
Relationship between repetitive behavior and
social/communication deficits
Present
Present
Absent
Present
... Whilst individuals with CdLS, FXS and RTS have a heightened likelihood of showing autistic traits compared to the general population [15,16], these groups show distinct profiles of these traits [17]. Individuals with CdLS show fewer repetitive behaviours but more frequent and greater communication difficulties than individuals with non-syndromic ASC [17], whereas individuals with FXS show an even profile of ASC-related social interaction, communication and repetitive behaviours that is a similar pattern but at lower levels compared to autistic individuals [18,19]. ...
... Individuals with CdLS show fewer repetitive behaviours but more frequent and greater communication difficulties than individuals with non-syndromic ASC [17], whereas individuals with FXS show an even profile of ASC-related social interaction, communication and repetitive behaviours that is a similar pattern but at lower levels compared to autistic individuals [18,19]. In contrast, the profile of autistic characteristics in individuals with RTS is defined more by restricted and repetitive behaviours than social and communication impairments [16]. These differences may be indicative of variability across aspects of social cognition that underpin the profiles of social behaviour and communication that are associated with ASC in these syndromes. ...
... This is the first study to characterise the development of a broad range of early social cognitive abilities in neurogenetic syndromes that have been shown to have atypical profiles of autistic traits [16][17][18] using a novel technique utilising a normatively scaled battery of robust and established behavioural tasks [27]. Findings indicate that individuals with CdLS, FXS and RTS demonstrated a pattern of delay and difference in the development of early social cognitive abilities relative to that observed in TD or AUT comparison groups. ...
Article
Full-text available
Background Cornelia de Lange (CdLS), Fragile X (FXS) and Rubinstein–Taybi syndromes (RTS) evidence unique profiles of autistic characteristics. To delineate these profiles further, the development of early social cognitive abilities in children with CdLS, FXS and RTS was compared to that observed in typically developing (TD) and autistic (AUT) children. Methods Children with CdLS ( N = 22), FXS ( N = 19) and RTS ( N = 18), completed the Early Social Cognition Scale (ESCogS). Extant data from AUT ( N = 19) and TD ( N = 86) children were used for comparison. Results Similar to AUT children, children with CdLS, FXS and RTS showed an overall delay in passing ESCogS tasks. Children with CdLS showed a similar degree of delay to AUT children and greater delay than children with FXS and RTS. The CdLS, FXS and RTS groups did not pass tasks in the same sequence observed in TD and AUT children. Children with CdLS ( p = 0.04), FXS ( p = 0.02) and RTS ( p = 0.04) performed better on tasks requiring understanding simple intentions in others significantly more than tasks requiring joint attention skills. Conclusions An underlying mechanism other than general cognitive delay may be disrupting early social cognitive development in children with CdLS, FXS and RTS. Factors that may disrupt early social cognitive development within these syndromes are discussed.
... There is also a growing body of literature showing that CdLS and RSTS's behavioral phenotypes are not stable over individual developmental trajectories. In adolescence and early adulthood, internalizing and externalizing disorders might arise, enriching the clinical picture of the patient with complexity, as well as, making healthcare even more time-consuming and complicated (Basile et al., 2007;Crawford, Waite, & Oliver, 2017;Waite et al., 2015). RSTS patients are likely to exhibit specific behavioral phenotypes, including anxiety, mood instability, compulsive, and aggressive behaviors, which worsen with age (Stevens, 2002;Stevens, Pouncey, & Knowles, 2011;Yagihashi et al., 2012). ...
... Our study is consistent with the literature and supports a positive association between autism spectrum disorder (ASD) traits and internalizing symptoms in individuals with genetic syndromes (Groves et al., 2021). Recent research estimated a prevalence rate of ASD and autistic-like behaviors ranging from 27% to 82% in CdLS (Ajmone et al., 2021;Basile et al., 2007;Bhyuian et al., 2006;Moss et al., 2008;Moss, Oliver, Arron, Burbidge, & Berg, 2009;Mulder et al., 2019;Oliver, Arron, Sloneem, & Hall, 2008;Richards, Jones, Groves, Moss, & Oliver, 2015), and approximately from 37% to 62% in RSTS (Ajmone et al., 2018;Stevens et al., 2011;Stevens, 2002;Waite et al., 2015). ...
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Background and aim: There is mounting evidence highlighting that Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome’s (RSTS) behavioral phenotypes are not stable over individual developmental trajectories and that several psychiatric disorders might arise with age. Our study aims to examine the specific hallmarks of psychopathology and behavioral phenotypes in four different age ranges: infancy and toddlerhood, early childhood, middle childhood, and adolescence, in both genetic syndromes. Method: The sample included 44 patients with CdLS (48% boys, age = 6.67 ± 4.36) and 31 with RSTS (48% boys, age = 6.89 ± 4.58) recruited through follow-ups. Cognitive, behavioral, and autism assessments were carried out with Griffith's scales or the Leiter-R, the Child Behavior Checklist, and the Child Autism Rating Scales 2. Multiple ANOVA 2x4 were run to outline behavioral phenotypic age-related syndromic markers and ANCOVA to value the weight of IQ and ASD-related traits on the psychopathological outcome. Results: Findings showed that anxiety is a crucial phenotypic hallmark, independent of IQ but associated with autistic traits, that increases from infancy to adolescence in both CdLS and RSTS. Conclusion and implications: Being aware of the developmental challenges that growing children are called to face is essential for drawing up proper standards of assessment turning into target age-related interventions, ensuring these patients personalized healthcare and improvement in life quality.
... Evidence has shown that clinical features in EP300 patients are less significant than in CREBBP patients, and notably that intellectual disability is generally milder (López et al., 2018). Regarding behavioural symptomatology, hyperactivity, peculiar abnormalities in expressive language competencies, attentional and motor difficulties, noise intolerance, and maladaptive and unusual behaviours (mainly selfmutilation) have been observed among individuals with RSTS (Hennekam et al., 1992;Stevens et al., 1990;Waite et al., 2015). Moreover, specific behaviours such as stereotypical motor behaviour and poor motor coordination, and specific features such as being overweight (Cazalets et al., 2017;Galéra et al., 2009), suffering from a mood disorder, and being on the obsessive-compulsive spectrum have been observed (Hellings, Hossain, Martin, & Baratang, 2002;Levitas & Reid, 1998). ...
... They noted that children with RSTS were more jovial and more socially interactive than children with an intellectual disability. Waite et al. (2015) compared children with RSTS to children with either Down syndrome, Fragile X syndrome, or Autism Spectrum Disorder (ASD) and found that children with RSTS had significantly higher scores than children with Down syndrome on stereotypical behaviours, compulsive behaviours, and verbal subscales. However, they did not differ from groups of children with ASD or Fragile X syndrome. ...
Article
Background: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomaly syndrome characterised by several typical somatic characteristics and by developmental disabilities with various degrees of severity. Focusing on children with RSTS, the aim of this study was to describe their psychomotor, cognitive, and socio-emotional developmental profiles. Method: Twenty-three children with RSTS (12 boys; 11 girls; mean chronological age: 4 years and 10 months) with severe intellectual disability (mean developmental quotient = 32.39) were recruited from an Expert Department of Medical Genetics. Developmental assessments were carried out with the Brunet-Lézine-Revised scale and the Social Cognitive Evaluation Battery. Results: The participants’ developmental profiles were characterised by heterogeneous psychomotor development, homogeneous cognitive and socio-emotional development, by more severe delays in expressive language, vocal imitation, and symbolic play skills, and by better developmental levels in socio-emotional abilities. Conclusions: Based on these atypical developmental profiles, early interventions should target the three most delayed abilities.
... In later adulthood this pattern changes again to a loss in interests and sometimes depression ( Fig. 3 and Supplementary Table 1). Our observations agree with previous ones [7,16,17] and highlight the need to follow up patients with RTS and, if necessary, refer to psychiatry. Moreover, our observations are similar to behavioural findings in other developmental disorders caused by disruptions of epigenetic regulator genes both regarding the high incidence of a specific pattern of rigid, repetitive, and inflexible behaviours and emotional dysregulation [18] but also age-dependent progression [19]. ...
Article
The existing knowledge about morbidity in adults with Rubinstein-Taybi syndrome (RTS) is limited and detailed data on their natural history and response to management are needed for optimal care in later life. We formed an international, multidisciplinary working group that developed an accessible questionnaire including key issues about adults with RTS and disseminated this to all known RTS support groups via social media. We report the observations from a cohort of 87 adult individuals of whom 43 had a molecularly confirmed diagnosis. The adult natural history of RTS is defined by prevalent behavioural/psychiatric problems (83%), gastrointestinal problems (73%) that are represented mainly by constipation; and sleep problems (62%) that manifest in a consistent pattern of sleep apnoea, difficulty staying asleep and an increased need for sleep. Furthermore, over than half of the RTS individuals (65%) had skin and adnexa-related problems. Half of the individuals receive multidisciplinary follow-up and required surgery at least once, and most frequently more than once, during adulthood. Our data confirm that adults with RTS enjoy both social and occupational possibilities, show a variegated experience of everyday life but experience a significant morbidity and ongoing medical issues which do not appear to be as coordinated and multidisciplinary managed as in paediatric patients. We highlight the need for optimal care in a multidisciplinary setting including the pivotal role of specialists for adult care.
... The first aim was to compare profiles of EF behaviours of individuals with CdLS, FXS, RTS and AUT between one another and to normative data from two-to-three-year-old TD children. Consistent with previous reports (Reid et al., 2017;Waite et al., 2015;Schmitt et al., 2019;Johnson, 2015) all syndrome groups showed high levels of executive dysfunction similar to AUT individuals. ...
Article
Full-text available
Background Individuals with genetic syndromes show unique profiles of repetitive behaviours and restricted interests (RRBs). The executive dysfunction account of RRBs suggests that in autistic (AUT) individuals executive function impairments underpin RRBs, but not communication and social interaction autistic characteristics. Aims To 1) describe profiles of behavioural manifestations of executive function (EF behaviours) and 2) explore the relationship between EF behaviours and autistic traits across individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and AUT individuals. Method Carers completed the Behavior Rating Inventory of Executive Function – Preschool Version and the Social Communication Questionnaire. Data reporting on 25 individuals with CdLS (Mage = 18.60, SD = 8.94), 25 with FXS (Mage = 18.48, SD = 8.80), 25 with RTS (Mage = 18.60, SD = 8.65) and 25 AUT individuals (Mage = 18.52, SD = 8.65) matched on chronological age and adaptive ability were included in analyses. Results All groups showed impairments across EF behaviours compared to two-to-three-year-old typically developing normative samples with no differences between groups. Different EF behaviours predicted RRBs in the syndrome groups with no associations found in the AUT group. Conclusions Syndrome related differences should be considered when developing targeted interventions that focus on EF behaviours and/or RRBs in these groups.
... Intellectual disability in RSTS is usually associated with an intelligence quotient (IQ) ranging from 25 to 79 (Hennekam et al., 1992;Lacombe et al., 1992;Levitas & Reid, 1998;Stevens et al., 1990), when an average IQ is 100 with average scores ranging from 85 and 115. Additionally, studies of behavioral symptomatology with or without contrast groups have shown abnormalities of children with RSTS, such as difficulty managing emotions, short attention span, motor stereotypies, more excitability and self-stimulation (Galéra et al., 2009), more difficulties in motor action planning and in oculomotor task performance (Cazalets et al., 2017), and a phenotypic profile of repetitive behaviors (Waite et al., 2015). However, they were also described as more jovial and socially interactive (Goots & Liemohn, 1977;Moss et al., 2016) and in comparison with either Down syndrome, Fragile X syndrome, or Autism Spectrum Disorder (ASD), had better abilities on verbal memory development . ...
Article
Background Cognitive and socio-emotional profiles of children with CREBBP-related Rubinstein-Taybi syndrome (RSTS 1), children with Autism Spectrum Disorder (ASD) with severe intellectual disability and developmental ages (DA) under 24 months, and typically developing (TD) children with similar DA were compared. Participants Thirty-one children with RSTS 1 (mean chronological age, CA = 59,8 months; 33−87) and thirty children with ASD, matched on CA and DA and developmental quotients (DQ), were compared to thirty TD children (CA ranged from 12 to 24 months). Methods Cognitive and socio-emotional developmental levels, DA and DQ were assessed with appropriated tests. Results More socio-emotional developmental similarities were observed between TD and RSTS 1 than between TD and ASD children. Clinical groups displayed similar developmental delays in cognitive (self-image, symbolic play, means-ends, and object permanence) and socio-emotional domains (language and imitation). Children with RSTS 1 exhibited higher developmental levels in behavior regulation, joint attention, affective relations, emotional expression domains, and a lower developmental level in spatial relations domain. Conclusions Common interventions centered on symbolic play, self-image, language, and imitation for both clinical groups, and differentiated interventions centered on spatial abilities for RSTS 1 children and on social abilities for ASD could be used by caregivers were suggested.
... Behavioral symptomatology includes hyperactivity, noise intolerance, attention and motor difficulties, idiosyncrasies, and maladaptive and unusual behaviors (primarily selfinjury) [9,[45][46][47]. In addition, specific behaviors are frequently found combining attentional difficulties, motor stereotypies, visio-spatial clumsiness, and visio-motor coordination difficulties [48,49]. ...
Article
Full-text available
The Rubinstein-Taybi syndrome (RSTS) is a rare congenital developmental disorder characterized by a typical facial dysmorphism, distal limb abnormalities, intellectual disability, and many additional phenotypical features. It occurs at between 1/100,000 and 1/125,000 births. Two genes are currently known to cause RSTS, CREBBP and EP300, mutated in around 55% and 8% of clinically diagnosed cases, respectively. To date, 500 pathogenic variants have been reported for the CREBBP gene and 118 for EP300. These two genes encode paralogs acting as lysine acetyltransferase involved in transcriptional regulation and chromatin remodeling with a key role in neuronal plasticity and cognition. Because of the clinical heterogeneity of this syndrome ranging from the typical clinical diagnosis to features overlapping with other Mendelian disorders of the epigenetic machinery, phenotype/genotype correlations remain difficult to establish. In this context, the deciphering of the patho-physiological process underlying these diseases and the definition of a specific episignature will likely improve the diagnostic efficiency but also open novel therapeutic perspectives. This review summarizes the current clinical and molecular knowledge and highlights the epigenetic regulation of RSTS as a model of chromatinopathy.
... Sociability is an umbrella term that encompasses a broad range of skills and behaviors that contribute to an individual's social competence. Most research on the components of sociability within genetic syndromes has focused on autistic traits (Galéra et al. 2009;Mulder et al. 2017;Grados et al. 2017;Moss et al. 2013b;Hogan et al. 2017;Waite et al. 2015;Davenport et al. 2016). Many genetic syndromes have been shown to evidence heightened levels of autistic traits but also show unique profiles of sociability that are not captured fully by diagnostic measures of autism (Moss et al. 2013b(Moss et al. , 2016. ...
Article
Full-text available
We directly assessed the broader aspects of sociability (social enjoyment, social motivation, social interaction skills and social discomfort) in individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and their association with autism characteristics and chronological age in these groups. Individuals with FXS (p < 0.01) and RTS (p < 0.01) showed poorer quality of eye contact compared to individuals with CdLS. Individuals with FXS showed less person and more object attention than individuals with CdLS (p < 0.01). Associations between sociability and autism characteristics and chronological age differed between groups, which may indicate divergence in the development and aetiology of different components of sociability across these groups. Findings indicate that individuals with CdLS, FXS and RTS show unique profiles of sociability.
Article
Rubinstein–Taybi syndrome (RTS) is a rare genetic syndrome associated with growth delay, phenotypic facial characteristics, microcephaly, developmental delay, broad thumbs, and big toes. Most research on RTS has focused on the genotype and physical phenotype; however, several studies have described behavioral, cognitive, social, and emotional characteristics, elucidating the behavioral phenotype of RTS. The reporting of this review was informed by PRISMA guidelines. A systematic search of CINAHL, Medline, and PsychINFO was carried out in March 2021 to identify group studies describing behavioral, cognitive, emotional, psychiatric, and social characteristics in RTS. The studies were quality appraised. Characteristics reported include repetitive behavior, behaviors that challenge, intellectual disability, mental health difficulties, autism characteristics, and heightened sociability. Findings were largely consistent across studies, indicating that many characteristics are likely to form part of the behavioral phenotype of RTS. However, methodological limitations, such as a lack of appropriate comparison groups and inconsistency in measurement weaken these conclusions. There is a need for multi-disciplinary studies, combining genetic and psychological measurement expertise within single research studies. Recommendations are made for future research studies in RTS.
Article
Rubinstein-Taybi syndrome (RSTS), also known as broad thumb-great toe syndrome or broad digits syndrome, is a rare autosomal dominant genetic disease. The main features of the patients are craniofacial dysmorphisms, skeletal malformations, and delay of growth and psychomotor development. In this case, the child has a typical RSTS specific face and growth retardation, with atypical indirect inguinalhemia. A heterozygous mutation, C. 4492 C>T (p. Arg1498Ter), was found in the exon of CREBBP gene by gene sequencing. It was a nonsense mutation, which leads to the premature termination of peptide synthesis. The mutation was not observed in the child's parents, which may be a de Novo mutation. The disease is lack of effective therapy so far.
Conference Paper
Background: Little is known about the stability of individual restricted and repetitive behaviors (RRBs) in children with autism spectrum disorders (ASD) (i.e., how commonly behaviors are lost or improve and how often they are acquired or worsen over time.) There is evidence that ‘repetitive sensorimotor’ (RSM) behaviors (e.g., motor mannerisms) follow different developmental trajectories than ‘insistence on sameness’ (IS) behaviors (e.g., rituals). Objectives: We examine the stability of individual RRBs over time in children with ASD, and which factors are associated with stability. Methods: Data were collected as part of a longitudinal study of toddlers referred for possible autism. There were 214 participants in the first cohort, 192 of whom were referred because of concerns about ASD. The nonspectrum developmental disorder (DD) referral group consisted of 22 developmentally delayed children who had never been referred for or diagnosed with autism. At each wave, children completed a battery of cognitive and diagnostic measures, and parents completed the Autism Diagnostic Interview-Revised. At ages 2, 5, and 9, each child was assigned a consensus best-estimate clinical diagnosis of autism, pervasive developmental disorder-not otherwise specified, or a nonspectrum developmental disorder. Results: Once children with ASD had a particular RSM behavior, they were likely to continue having it, and children who did not have the behavior often acquired it. However, these behaviors often improved in children with higher nonverbal IQ (NVIQ) scores and/or milder ASD. Many children who did not have IS behaviors at a young age acquired them as they got older, whereas children who had these behaviors sometimes lost them. Trajectories of IS behaviors were not closely related to diagnosis and NVIQ. Conclusions: Individual RRBs show different patterns of stability in children with ASD, based partly on the ‘subtype’ they belong to. Young children with low NVIQ scores often have persistent RSM behaviors.
Article
Children admitted to an institution for severely subnormal patients and subsequently diagnosed as schizophrenic were compared with a group of children of the same age, sex and I.Q. in the same hospital, who were free from schizophrenic characteristics. The two groups showed a similar amount of exploration of and orientation towards stimuli. Though the experimental group gave the same amount of social response and approach behaviour as the controls, the former also tended to retreat from the experimenter at times. Significantly more children talked in the control than in the experimental group. Activity of a non-object orientated kind was more frequently observed in the psychotic children than in the controls. While the amount of orienting behaviour varied according to the various stimulus situations in both groups, activity which did not occur in response to external stimuli did not.
Article
This natural observation study was designed to evaluate hypothesized elevated 'attention-seeking' and preference for adult attention in Smith-Magenis syndrome. Ten children with Smith-Magenis syndrome were observed across one school day, together with an age matched sample of 10 children with Down syndrome. Levels of attention given to, and vigilance for, adults and peers were recorded and compared. Sequences of behaviour were analyzed to evaluate the temporal relationships between giving and receiving attention during adult-child interactions. Compared to children with Down syndrome, children with Smith-Magenis syndrome gave preferential attention to adults and looked towards adults significantly more than they looked towards peers. Sequential analyses revealed that while children with Smith-Magenis syndrome did not initiate interactions with adults more than children with Down syndrome did, reciprocity between child and adult social behaviours in Smith-Magenis syndrome within interactions was compromised. This less synchronous sequence of child and adult interactions in Smith-Magenis syndrome may be the result of children with Smith-Magenis syndrome attempting to initiate interaction at times when it is unavailable. The marked preference for interacting with adults over peers in Smith-Magenis syndrome indicates atypicality of social interaction in this syndrome.