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The fractal dimension approach in posture: a

comparison between Down and PraderWilli syndrome
patients
ab

ac

Veronica Cimolin , Manuela Galli , Chiara Rigoldi , Graziano Grugni , Luca Vismara ,
e

Shirley Aparecida Fabris de Souza , Luca Mainardi , Giorgio Albertini & Paolo Capodaglio
a

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Italy

Orthopaedic Rehabilitation Unit and Clinical Lab for Gait Analysis and Posture, Ospedale
San Giuseppe, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Italy
c

IRCCS San Raffaele Pisana, Tosinvest Sanit SPA, Roma, Italy

Unit of Auxology, Ospedale San Giuseppe, Istituto Auxologico Italiano, Piancavallo (VB),
Italy
e

Department of Physiotherapy, Hospital Universitario de Londrina, Londrina State

University, Londrina, PR, Brazil
Published online: 29 Jan 2013.

To cite this article: Veronica Cimolin, Manuela Galli, Chiara Rigoldi, Graziano Grugni, Luca Vismara, Shirley Aparecida
Fabris de Souza, Luca Mainardi, Giorgio Albertini & Paolo Capodaglio (2014) The fractal dimension approach in posture:
a comparison between Down and PraderWilli syndrome patients, Computer Methods in Biomechanics and Biomedical
Engineering, 17:14, 1535-1541, DOI: 10.1080/10255842.2012.753068
To link to this article: http://dx.doi.org/10.1080/10255842.2012.753068

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Computer Methods in Biomechanics and Biomedical Engineering, 2014

Vol. 17, No. 14, 1535 1541, http://dx.doi.org/10.1080/10255842.2012.753068

The fractal dimension approach in posture: a comparison between Down and Prader Willi
syndrome patients
Veronica Cimolina,b*, Manuela Gallia,c, Chiara Rigoldia, Graziano Grugnid, Luca Vismarab, Shirley Aparecida Fabris de
Souzae, Luca Mainardia, Giorgio Albertinic and Paolo Capodagliob
a

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Italy; bOrthopaedic Rehabilitation Unit and Clinical
Lab for Gait Analysis and Posture, Ospedale San Giuseppe, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Italy; cIRCCS San
Raffaele Pisana, Tosinvest Sanita` SPA, Roma, Italy; dUnit of Auxology, Ospedale San Giuseppe, Istituto Auxologico Italiano,
Piancavallo (VB), Italy; eDepartment of Physiotherapy, Hospital Universitario de Londrina, Londrina State University, Londrina, PR,
Brazil

Downloaded by [New York University] at 03:51 03 October 2014

(Received 16 July 2012; final version received 22 November 2012)

The suitability of new dynamic system analysis was investigated to compare postural control in Prader-Willi syndrome
(PWS) and Down syndrome (DS) patients. Time-domain, frequency-domain parameters and fractal dimension (FD) of
centre of pressure (CoP) were computed in maintaining normal standing on a force platform in 20 DS and 13 PWS patients,
compared to 26 obese (obese control group, OCG) and 20 healthy individuals (healthy control group, HCG). DS and PWS
showed greater displacements along both directions and longer sway path (SP) parameter than HCG and OCG, with
statistical differences between PWS and DS for anteroposterior displacement and SP. DS used higher frequency strategy
when compared to PWS, OCG and HCG. Both DS and PWS were characterised by greater values of FD than OCG and
HCG, with higher values in DS. The analyses in frequency domain and of the dynamic nature of CoP suggest that DS
patients are characterised by a more complex and irregular signal than PWS patients.
Keywords: posture evaluation; fractal dimension analysis; centre of pressure; Prader-Willi syndrome; Down syndrome

1.

Introduction

Prader-Willi syndrome (PWS) and Down syndrome (DS)

are two different chromosomal disorders characterised by
some common clinical features, such as obesity, muscular
hypotonia, ligament laxity and mental retardation. Their
ability to sit, kneel, stand and walk is compared with the
ability of children of the same age, and in adult life,
although hypotonia does not progress, the progressive
effects of obesity on joints produce a cautious abnormal
gait and posture (Davis and Kelso 1982; Butler 2006;
Goeltz 2006; Cimolin, Galli, Grugni, et al. 2011). Since
balance is a key function for performing daily life tasks,
investigating this capacity appears necessary to define the
functional profile in the PWS and DS population to be able
to plan appropriate rehabilitation interventions.
In general, the integrity of the postural control system
is evaluated by analysing the centre of pressure (CoP) with
static posturography. The effectiveness of the postural
control system has been related to the magnitude of
displacements of the CoP, whereas parameters related to
the velocity of CoP are generally associated with
posturographic activity to achieve this level of stability
(Myklebust et al. 1995). Postural control is often assessed
as a variation in the ground reaction forces during quite
standing and generally the analysis of the application point

*Corresponding author. Email: [email protected]

q 2013 Taylor & Francis

of the resultants of these forces, the CoP, is conducted as a

function of time. However, from a physiological point of
view, the information obtained by the common CoP timedomain analysis cannot be univocally interpreted. The
CoP represents in fact the sum of various neuromusculoskeletal components acting at different joint
levels and its time series is two dimensional or planar.
Although the two components of the signal, anteriorposterior and mediolateral, are generally analysed separately,
they represent the output of a unique integrated system. In
addition, posture can be considered to be a dynamic
stability of a continuously moving body. For this reason,
human movement is not separated into a perfect static state
(posture) and a dynamic state (movement), as posture and
movement could be considered to be adaptively and
flexibility integrated. As a consequence, the utility of static
posturography in clinical practice needs for reliable
approaches in order to extract physiologically meaningful
information from stabilograms (Myklebust et al. 1995;
Manabe et al. 2001). During the last decades, various new
mathematical tools have been used to better characterise
the nonlinear and dynamic features of postural variability.
Among these methods, the fractal dimension (FD)
approach has been proposed in order to better describe
the dynamic patterns of biological signals (Myklebust et al.

1536
Table 1.

V. Cimolin et al.
Characteristics of the study groups.

Participants (M/F)
Age (years)
Height (m)
BMI (kg/m2)
Foot length (mm)

PWS

DS

OCG

HCG

13 (6/7)
32.4 ^ 4.2
1.52 ^ 0.8*, **
40.3 ^ 6.6*
209.6 ^ 13.1*

20 (11/9)
29.1 ^ 8.1
1.51 ^ 0.1*, **
35.8 ^ 6.2*
219.8 ^ 14.7*

26 (15/11)
34.2 ^ 10.7
1.67 ^ 0.9
40.6 ^ 4.6*
222.5 ^ 10.1*

20 (10/10)
31.4 ^ 9.6
1.73 ^ 0.5
22.8 ^ 3.2
239.9 ^ 11.4

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Notes: PWS, Prader Willi syndrome; DS, Down syndrome; OCG, healthy control group; HCG, healthy control group. Data are expressed as median and quartile range.
*p , 0.05, compared with HCG; **p , 0.05, compared with OCG.

1995; Peng et al. 2000; Manabe et al. 2001; Doyle et al.

2005), representing a relative measure of the number of
elemental units fabricating a pattern. Previous studies
(Myklebust et al. 1995; Manabe et al. 2001; Doyle et al.
2005) have demonstrated that fractal analysis represents a
reliable method to highlight specific characteristics of
balance control. FD can in fact be used to quantify the
complexity of CoP trajectory: a change in FD may indicate
a change in control strategies for maintaining quiet stance
and in the stability of the system: the higher FD, the more
complex the CoP signal (Doyle et al. 2005). In literature,
only few studies have been conducted using the FD
technique to investigate posture and they were conducted
on Parkinson and ataxia (Manabe et al. 2001), on PWS
(Cimolin, Galli, Rigoldi, et al. 2011) and on DS patients
(Rigoldi et al. 2012). The authors found FD to be more
sensitive in the evaluation of postural instability in these
conditions than the traditional stabilometric analysis
conducted using time-domain analysis.
According to the need for a deeper investigation of
postural instability in DS and PWS and to the promising
application of an FD approach on PWS patients, our goal
was to quantitatively compare postural control in adult
PWS and DS, not only considering the traditional methods
of CoP analysis in time-domain, but also using the
frequency-domain technique and the FD approach, in
order to evaluate if these methods could offer additional
and clinically useful information.
The main limitation of previous studies on PWS and
DS was that they compared results to a normal weight
control group, without taking in consideration the possible
influence of obesity on postural ability. There is evidence
that body weight is a strong predictor of postural stability
(Hue et al. 2007), with obesity-associated postural
perturbations appearing in adolescence (McGraw et al.
2000). In particular, obesity has been associated with
greater forward displacement of the CoP during dynamic
standing balance activities (Berrigan et al. 2006). Based on
such considerations, we included also a control group
composed of healthy obese individuals.

2. Methods
2.1 Participants
In this study, we enrolled 20 DS and 13 PWS adult patients
matched for age, height and body mass index (BMI;
kg/m2) (Table 1); some of these patients were previously
included in another study (Cimolin, Galli, Grugni, et al.
2011). DS patients were all referred to the IRCCS San
Raffaele Pisana, Tosinvest Sanita`, Roma, Italy. The
distribution of chromosomal anomalies is pure trisomy 21
in all of the DS patients. PWS patients had been
periodically hospitalised at the San Giuseppe Hospital,
Istituto Auxologico Italiano, Piancavallo (VB), Italy. All
patients showed the typical PWS clinical phenotype
(Holm et al. 1993). Cytogenetic analysis was carried out in
all participants; 10 had interstitial deletion of the proximal
long arm of chromosome 15 (del15q11 q13). Moreover,
uniparental maternal disomy for chromosome 15 (UPD15)
was found in three subjects.
All DS and PWS subjects showed mild mental
retardation but were able to understand and complete the
test. All participants had to be able to maintain their
equilibrium independently without assistance or with the
use of crutches, walkers or braces. They were sedentary
people and they did not typically take part in sports
activities.
Two different groups of subjects were specifically
recruited for this study and served as controls (Table 1).
The first group included 26 obese subjects (obese control
group, OCG), and the second group included 20 healthy
subjects with a BMI ranging from 19.3 to 25.4 (healthy
control group, HCG). All PWS and control obese patients
were found with normal values in main laboratory tests,
including adrenal and thyroid function. Exclusion criteria
for HCG included prior history of cardiovascular,
neurological or musculoskeletal disorders.
All participants were free from conditions associated
with impaired balance and individuals with vision
loss/alteration, vestibular impairments, neuropathy, as
detected by the clinical examination and those who
reported symptoms related to intracranial hypertension,
were excluded. The study was approved by the Ethics
Committees of the two Institutes for DS, PWS patients and
OCG, respectively. Written informed consent was

Computer Methods in Biomechanics and Biomedical Engineering

obtained by the parents or, when applicable, by the
patients.

Downloaded by [New York University] at 03:51 03 October 2014

2.2

Experimental set-up

Static posturography was conducted on a non-movable

force plate (Kistler, CH; acquisition frequency: 500 Hz).
The participants were asked to stand for 30 s on the force
platform, their feet placed with an angle of 308 in a fixed
and standardised position and their arms at their sides. The
individuals were instructed to maintain normal standing
balance, undisturbed stance with eyes opened looking at a
black target 1.5 m far away (a circle with a diameter of
6 cm) which was positioned vertically to be in the patients
direct line of sight, in order to standardise the trials. For
each subject, a sequence of three trials was carried out at
10-min intervals, in order to minimise the possibly
confounding effect of fatigue.

2.3 Data analysis

The outputs of the force platform allowed us to compute
the CoP time series in the A/P direction (CoPAP) and the
M/L direction (CoPML). The output of the platform was
processed to compute quantitative parameters in time
domain and frequency domain as well as using the FD
technique. The computed parameters computed as for
time-domain and frequency-domain analyses were listed
in Table 2.
All the parameters computed using the time-domain
analysis were normalised to the participants height
(expressed in metres) and to their foot length (expressed in
millimetres). In fact, short feet are one of the typical
features of PWS (Hudgins and Cassidy 1991) and DS
patients (Diamond et al. 1981). It has been shown that the
base of support, as calculated from the foot length, is one
Table 2.

1537

of the most relevant biomechanical variables in the

postural analysis (Chiari et al. 2002).
As for FD parameter, it was computed on the image of
CoP trajectory using the box-counting method (Feder
1988). Briefly, let us superimpose a square grid on the
image, being 1 the edge size of each square, and let us
indicate as N(1) the number of squares needed to fully cover
the image. It can be shown that, in the limit 1 ! 0, we have
N1 ,

1
;
1D

where D is known a box-counting FD. The quantity D can

be estimated by computing N(1) for different values of grid
size 1. According to relation (1), this yields an array of
points in log log space that can be fitted with a straight line
whose negative slope provides an estimate of the FD value.
This parameter allows estimating the stabilometry pattern
more quantitatively than the traditional methods. A signal
with an FD equal to 1 would indicate a completely
stationary signal over time, whereas an FD of 2 would
indicate a signal that oscillates equally about a central
tendency over time. This value is higher when the picture is
more complex. In particular, this method allows the bidimensional analysis, not used in the previous studies
which generally used FD approach in one dimension (for
postural analysis in the anterioposterior and mediolateral
directions, separately) (Blaszczky and Klonowsky 2001;
Manabe et al. 2001; Doyle et al. 2005).

2.4

Statistical analysis

All the previously defined parameters were computed for

each participant and then the median and quartile range
values of all indexes were calculated for each
group. Kolmogorov Smirnov tests were used to verify if
the parameters were normally distributed; the parameters
were not normally distributed, so we used analysis of

Descriptors of the parameters computed from time-domain and frequency-domain analyses of CoP.

Parameters computed from time-domain and frequency-domain

analyses
Time-domain parameters a
RANGEAP and RANGEML (1/m)
Sway path (SP) (1/m)
Frequency-domain analysis b
fML and fAP

The range of CoP displacement in the A/P direction (RANGEAP index)

and the M/L direction (RANGEML index), expressed in mm and
normalised to subjects height (m) and foot length (mm)
The total CoP trajectory length, expressed
in mm and normalised to subjects height (m) and foot length (mm)
The centre frequency of the main spectral peak of the P spectrum
in mediolateral (fML index) and anteroposterior direction
(fAP index)

The anteroposterior and mediolateral coordinates of the CoP trajectory underwent a post-acquisition filtering using a low-pass filter with a cut-off frequency of 10 Hz (Schmidt
et al. 2002).
The signals were first down-sampled (anti-aliasing filter) at 10 Hz. The analysis was performed using parametric estimators based on autoregressive (AR) modelling of the data
(Galli et al. 2008).
b

1538
Table 3.

V. Cimolin et al.
Postural parameters of the study groups.

Time-domain parameters
RANGEAP (1/m)
RANGEML (1/m)
SP (1/m)
Frequency-domain parameters
fAP (Hz)
fML (Hz)

PWS

DS

OCG

HCG

0.06 (0.03), *, **
0.07 (0.02)*, **
2.79 (0.89), *, **

0.05 (0.02)*, **
0.06 (0.02)*, **
4.29 (0.82)*, **

0.03 (0.01)*
0.03 (0.01)
0.72 (0.86)

0.02 (0.01)
0.03 (0.02)
0.51 (0.98)

0.10 (0.09)
0.13 (0.12)

0.31 (0.23)*, **
0.22 (0.18)*

0.10 (0.09)
0.19 (0.14)

0.16 (0.16)
0.12 (0.15)

Notes: PWS, Prader Willi Syndrome; DS, Down syndrome; OCG, obese control group; HCG, healthy control group. Data are expressed as median and quartile range. The
values of time-domain parameters are normalised for the subjects height and foot length. p , 0.05, PWS group versus DS group; *p , 0.05, compared with HCG; **p , 0.05,
compared with OCG.

Downloaded by [New York University] at 03:51 03 October 2014

variance for non-parametric (Kruskal Wallis) data

followed by a post hoc range analysis. P-Values less
than 0.05 were considered significant.

3.

Results

In Table 1, the clinical characteristics of DS, PWS, OCG

and HCG are reported. Age was not significantly different
among groups. BMI, weight and foot length were similar
in DS, PWS and OCG, but significantly different when
compared to HCG. The height was similar between PWS
and DS participants and lower in comparison with OCG
and HCG.
Although our first aim was to acquire at least three
trials for each participant, the presence of alert state and
the decreased cooperation and concentration in our
patients did not allow acquiring them in all individuals;
for this reason, the data presented were computed starting
from the first trial of each patient.
The data obtained using time-domain parameters
confirmed previous findings as for the comparison between
PWS and DS (Cimolin, Galli, Grugni, et al. 2011). Both DS
and PWS individuals showed greater displacements along
both the anteroposterior and mediolateral directions
(RANGEAP and RANGEML) and longer sway path (SP)
parameter when compared to HCG and OCG (Table 3). In
particular, PWS and DS were statistically different in terms
of RANGEAP and SP parameters, and no alterations were
found in terms of RANGEML. HCG and OCG were
characterised by similar values ( p . 0.05).
The frequency-domain analysis showed that while
PWS were similar to all healthy participants (to both OCF
and HCG), the DS evidenced higher value both in
anteroposterior (fAP parameter) and mediolateral (fML
parameter) directions when compared to PWS and the two
control groups. These results showed that while PWS,
OCG and HCG use the same frequency in posture
maintenance, the DS used higher frequency in all
directions (Table 3).
FD parameter evidenced that both DS and PWS were
characterised by greater values in comparison with OCG

Figure 1. Median (quartile range) of FD parameters for the

study groups (PWS, Prader Willi syndrome; DS, Down
syndrome; OCG, obese control group; HCG, healthy control
group). p , 0.05, PWS group versus DS group; *p , 0.05,
compared with HCG; **p , 0.05, compared with OCG.

and HCG, with DS showing higher values than PWS. OCG

and HCG displayed a signal with an FD close to 1, with no
statistical differences; on the contrary, DS and PWS were
characterised by higher FD values, indicating a more
complex and irregular signal over time (Figure 1), more
accentuated in DS ( p , 0.05, in the comparison between
PWS and DS).

4.

Discussion

This comparative study quantified postural parameters in

patients affected by DS and PWS, integrating a traditional
method (time-domain analysis) with the frequency domain
and FD technique. Our aim was to ascertain whether these
relatively new approaches would add relevant clinical
information to the traditional approach. The characterisation of postural capacity appears a key element for
depicting the functional profile of these populations, who
yield reduced balance and greater risk of fall than healthy
individuals (Finlayson et al. 2010) increased in presence of

Downloaded by [New York University] at 03:51 03 October 2014

Computer Methods in Biomechanics and Biomedical Engineering

obesity (Fjeldstad et al. 2008; Menegoni et al. 2009). The
literature on this topic is focused mainly on the data
analysis using the time-domain method, and few clinical
applications are present (Manabe et al. 2001; Cimolin,
Galli, Rigoldi, et al. 2011; Rigoldi et al. 2012) using the
frequency-domain and FD technique. In addition, the
studies conducted on PWS and DS with traditional
techniques did not take into consideration the effect of
obesity on postural control, as generally the comparisons
were conducted versus normal weight control group and
not obese individuals.
Our results are in line with previous studies using the
time-domain analysis (range of sway in AP and ML
directions and the total trajectory length): PWS and DS
showed a higher range of oscillations in both AP and ML
directions than HCG and OCG, suggesting generally
poorer balance. PWS and DS differed only in AP
displacement, lower in DS and higher in PWS, with
significant disparities in the length of CoP displacement,
higher in DS when compared with those in PWS. The
lower value of CoPAP oscillations in DS may be related to
their higher hip stiffness as compared to PWS. Interestingly, even if DS showed CoP oscillations close to PWS in
the ML direction and lower in AP, their CoP trajectory
length was significantly higher than PWS. We can,
therefore, hypothesise that the two syndromes are
characterised by different CoP velocities, faster in DS
than PWS. This hypothesis was confirmed by the
frequency-domain approach, which demonstrated that
DS was characterised by higher frequency in the two
directions. Our results showed, in fact, that although PWS
patients showed frequency parameters close to OCG and
HCG, DS were characterised by values of frequency
higher than the other groups considered in this analysis.
This result is in line with the literature on postural control
in DS individuals (Galli et al. 2008).
As for the FD parameters, our results showed that
both DS and PWS were characterised by higher values
than OCG and HCG, with DS higher than PWS. As the
nonlinear approach used to compute FD takes into
account the dynamic of the signal, these values are
indicators of the complexity of the stabilometric pattern
in postural maintenance in these individuals, with DS
showing a more complex and irregular signal. The higher
FD values in our patients may also be interpreted as an
inability to synergically modulate the three systems (i.e.
visual, vestibular and somatosensory) involved in
maintaining posture. Our body is consistently exposed
to external perturbations, which we try to counteract by
integrating the real-time inputs and the prediction system
based on previous inputs. The information given by the
nonlinear approach can well describe this mechanism and
our data reflect the difficulties encountered by our
patients, and particularly accentuated in DS, in adapting
to this process. We can assume that these difficulties may

1539

be related also to the different cognitive profiles of these

two syndromes. PWS patients are, in fact, generally
characterised by mild cognitive limitations (Dykens et al.
2000) and by better intellectual performances than DS
individuals; these different profiles may lead to different
ability to modulate the systems involved in maintaining
posture which is greater in PWS with respect to DS
individuals.
We demonstrated in previous studies (Cimolin, Galli,
Vismara, et al. 2011) that both PWS and DS patients are
characterised by unchanged postural stability when eyes
are open and closed, showing that their balance is not
influenced by visual input. The authors hypothesised that
proprioception is prevalent over visual input in postural
control in DS and PWS. Such abnormal modulations of the
systems involved in balance maintenance are confirmed by
the result obtained using the FD approach.
An important finding of this study is related to the
effect of obesity on postural control. We observed, in fact,
that the presence of differences between pathological
groups (PWS and DS group) and OCG in terms of all
analysed parameters leads to the consideration that
overweight, which is one of the distinctive features in
both PWS and DS, does not directly influence the postural
maintenance in these two pathological states.
Our analysis showed that both PWS and DS patients
yield a particularly impaired balance capacity, with DS
individuals affected more than the PWS group. It is
important to underline that this consideration is not clearly
evident by the traditional parameters obtained with the
time-domain approach but it is shown in particular by the
frequency-domain and fractal method, which better
explained the postural strategy in the two pathological
states.
These results are important from a clinical point of
view, as quantitative characterisation of postural strategy
in PWS and DS may serve as a basis to develop,
differentiate and enhance the rehabilitative options,
indicating that DS individuals need a more intensive
rehabilitative programme in comparison with PWS
individuals. In particular, as we previously demonstrated
(Galli et al. 2008; Cimolin, Galli, Vismara, et al. 2011) that
balance is not influenced by visual input and that
proprioception may be prevalent over visual input in the
development and setting of postural control system in DS
and PWS, the rehabilitative programme should also
consider somatosensory exercises, particularly in DS
patients, in addition to improving hypotonia, muscle
strength, weight loss and motor control by proprioceptive
training.
Based on our results, the frequency domain and FD
approach seems to add relevant information to the timedomain analysis of the CoP. These analyses, considering
the non-stationary nature of CoP signal, showed
peculiarities in posture maintenance which were not

Downloaded by [New York University] at 03:51 03 October 2014

1540

V. Cimolin et al.

evident solely from the traditional ones. However, it is not

a completely clear FD result in terms of postural control,
particularly from a clinical point of view. The FD values
may be interpreted as an inability to synergically modulate
the three systems (i.e. visual, vestibular and somatosensory) involved in maintaining posture. The human body is
continuously exposed to external perturbations, which we
try to counteract by integrating the real-time inputs and the
prediction system based on previous inputs. On the other
hand, a more complex stabilometric pattern could be also
interpreted as a characteristic of a successful vigilant
strategy to keep balance. Both interpretations can be
correct but the question is then how to decide which one is
the most appropriate one in a case at hand and the debate is
still open. More work is needed to identify the correct
physiological interpretation of this parameter in a given
condition. In addition, it is important to underline that an
effort should be made to try the computational method;
while at the moment time-domain and frequency-domain
parameters are easily obtained using the user-friendly
software for postural data analysis generally present in
clinical settings, the computation of FD parameter is not
yet obtained as it needs specific competencies.
The strength of this study could be twofold: first, the
obtained results demonstrated that noteworthy information
from a clinical point of view can be obtained using
postural analysis, which is a user-friendly assessment
using just a force platform, without specific subjects
needing to prepare, and without requiring them to retain
their underclothes. Secondly, the comparative analysis
was carried out not only with normal weight but also with
obese individuals, in order to highlight the role of weight
and its influence on postural maintenance.
This study has some limitations. A low number of
participants enrolled, particularly PWS, which resulted
in limited strength of the clinical and statistical findings;
it should however be reminded that PWS is a rare
condition and that therefore enrolment of those patients
is difficult. In addition, although we tried to acquire
more than one trial the results presented in this study
refer to only one trial, due to the subjects intrinsic
factors at the moment of the trial acquisitions; a stricter
analysis should be conducted considering more than one
trial. Another bias is that participants were not compared in
terms of orthopaedic characteristic, degree of muscle
hypotonia and weakness and ligament laxity, and also
cognitive impairment had not been measured nor compared
between groups.

Declaration of interest
The authors do not have any conflicts of interest or financial
interest. All authors attest and affirm that the material within has
not been and will not be submitted for publication elsewhere.

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