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Prader–Willi syndrome psychosocial profile in an Egyptian sample: a descriptive study

Ali, Dalia H.; Effat, Safia M.; Afifi, Hanan; El Shakankirey, Sarah

Middle East Current Psychiatry: April 2014 - Volume 21 - Issue 2 - p 95–105
doi: 10.1097/01.XME.0000444128.39964.77
Original articles
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Background Maladaptive behaviors and cognitive impairment in patients with Prader–Willi Syndrome can affect long-term functioning of patients and their family. Understanding difficulties underlying the maladaptive behavior allow better management. Few or no studies were conducted on the psychological aspect of this syndrome in Egypt. Available studies world wide suggested that the main problem in this syndrome is cognitive and behavioral; tremendous improvement in clinical picture has been reported through early diagnosis and management.

Objective The aim of the study was to evaluate the psychosocial behavioral deviations and the cognitive functions in a sample of Egyptian children with Prader–Willi syndrome.

Patients and methods From a cross-sectional descriptive study conducted in the National Research Centre, we included 15 of the 72 patients of both sexes with age range of 5–15 years, fulfilling the diagnostic threshold of the modified list of Prader–Willi criteria. Detailed cytogenetic analysis was performed by conventional cytogenetic analysis of peripheral blood lymphocytes and fluorescent in-situ hybridization. Cognitive and psychological profile of all patients were assessed by: (a) Wechsler Intelligence Scale for Children, (b) Child Behavior Checklist for ages 4–18, (c) Conners’ Parent Rating Scale-Revised; long version, and (d) Childhood Autism Rating Scale.

Results Patients had a mean age of 8 years (±2.19 SD). A total of 66.7% of the patients showed positive deletion, 100% of the patients were mentally subnormal, and 26.3% had autistic features. High prevalence of inattention, hyperactivity, anxiety, and social, cognitive, and behavioral problems were evident in the patients, with more frequency and severity in nondeletion patients.

Conclusion Cognitive and psychological challenges are a fixed part of the Prader–Willi Syndrome patients’ profiles. Some differences were found within different genotypes of our study group.

aDepartment of Neuropsychiatry, Institute of Psychiatry, Ain Shams University

bDepartment of Genetic Research, National Research Centre, Cairo, Egypt

Correspondence to Dalia H. Ali, MD, PhD, Department of Neuropsychiatry, Institute of Psychiatry, Ain Shams University, Cairo, Egypt Tel: +20 966 050 392 8802; fax: +0029965620000(2837); e-mail: daliahegazy74@yahoo.com

Received October 1, 2012

Accepted January 16, 2014

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Introduction

Prader–Willi syndrome is a complex, multisystem disorder that was first described by Langdon Down in 1887 and was reported by Prader et al. in 1956 1. The major clinical features of the syndrome include recognizable pattern of dysmorphic features with assortment of physical, cognitive, and behavioral/psychiatric disturbances 1.

Aggression, stubbornness, arguing, lying, skin picking, obsessions, food seeking and/or stealing 2, autistic spectrum disorders, attention deficit hyperactivity, and even psychosis have also been recognized 3,4.

The genetic basis of Prader–Willi Syndrome (PWS) is caused by the absence of expression of the paternally active genes in the PWS critical region on 15q11–q13. In ∼50–70% of individuals, this is the result of interstitial deletion of the proximal portion of the long arm of chromosome 15. In a further 15% individuals, a submicroscopic deletion can be demonstrated by molecular means. The remaining 25–30% of individuals with PWS, without a chromosome deletion, have been shown to have maternal uniparental disomy (UPD) where both PWS critical regions of 15q11–q13 are maternal in origin, which is functionally equivalent to a deletion type, as the paternally inherited allele of this critical region of 15q11–q13 is the only expressed because the genes on the maternal chromosomes 15 are virtually not expressed (inactivated through imprinting) 5.

Some psychosocial behaviors and neurodevelopmental disorders have been linked to certain genotypes of PWS 6. Pathognomonic cognitive and behavioral findings may help in the differentiation of children with PWS from all other causes of obesity and mental retardation. Defining these problems is essential in the management plan and proper care of the patients, as management focuses mainly on addressing the consequences of the syndrome 7.

Prader–Willi Syndrome is a complex genetic disorder that is not widely known in Egypt, where research is lacking. It is usually undiagnosed, and this results in faulty or unsatisfactory management of affected individuals. Many studies abroad suggested that the main problem in this syndrome is cognitive and behavioral, and that the clinical picture improves tremendously through early diagnosis and behavioral modification.

Hence, we planned this research aiming to study the psychosocial behavioral deviations and the cognitive functions in a sample of Egyptian children with Prader–Willi syndrome. A better understanding of this complex disorder through a closer look on the problematic issues in these children may help in future management and in tailoring suitable multidisciplinary rehabilitation program for the affected individuals.

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Patients and methods

Design and site of the study

This study was a cross-sectional descriptive study conducted between 2008 and 2012 in the National Research Centre (NRC), which is one of the main genetic centers in Egypt. It is considered one of the largest genetic centers in the Middle East, serving as a referral center to all patients suspected to have genetic diseases of all subspecialties. The patients were subjected to complete physical, psychological, and genetic assessment and intervention accordingly, including medical, hormonal, psychological, dental, audiological, and phoniatric care services.

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Ethical issues

The design and methods of the study were approved by the ethical and scientific committee of Department of Psychiatry, Faculty of Medicine, Ain Shams University and its corresponding in the NRC. All patients and their legal guardians were informed about the details of the study and gave informed consent before being involved in the study.

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Patients

We screened the patients referred to the outpatients’ clinic of Clinical Genetics Department, NRC for 5 years (2008–2012) for obesity, hypotonia, delayed mental development, and hypogonadism. Seventy-two patients had at least three of these findings. Of these patients, only 15 patients of both sexes were included in the study who fulfilled the diagnostic threshold of the modified list of Prader–Willi criteria 8 as shown in Table 1. Their ages ranged from 5 to 15 years. We excluded patients who did not fulfill the above-mentioned criteria and non approving candidates.

Table 1

Table 1

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Tools and procedures

All patients were evaluated by an experienced physician trained as genetic researcher and a trained psychologist by the following: (a) diagnosis of PWS using the modified list of clinical diagnostic criteria 8, (b) complete history taking including personal, medical, and developmental history, (c) Pedigree construction and analysis with special emphasis on similarly affected family member(s), (d) Meticulous clinical examination of all body systems to detect any system abnormality, and (e) essential anthropometric measures including height, weight, and head circumference. Detailed cytogenetic analyses were performed by conventional cytogenetic analysis of peripheral blood lymphocytes 9 and fluorescent in-situ hybridization (FISH), using a single locus SNRPN probe to detect the deletion of SNRPN locus on chromosome 15q 10, to confirm the diagnosis and to categorize our patients into FISH positive (deletion type) and FISH negative or nondeletion type. Furthermore, we assessed all patients’ cognitive and psychological profile by: (a) Wechsler Intelligence Scale for Children 11, (b) Child Behavior Checklist for ages 4–18 (CBCL 4–18) 12, (c) Conners’ Parent Rating Scale-Revised; long version 13, and (d) Childhood Autism Rating Scale (CARS) 14.

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Tools for cognitive and psychological assessment

The modified list of Prader–Willi diagnostic criteria 8

The diagnosis of Prader–Willi syndrome is highly likely in children younger than 3 years with five points (three from major criteria) or in those older than 3 years with eight points (four from major criteria) as in Table 1.

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Wechsler Intelligence Scale for Children 11

The test has been proved to be adequately reliable and valid for both clinical and research purposes through many years of research and validation in assessing children’ intellectual abilities. This can be performed through a collection of 13 distinct subtest divided into two scales – a Verbal Scale and a Performance Scale.

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Revised Behavior Problem Checklist 12

It is used to record the children’s competencies and problems as reported by their parents in the form of dimensions or syndromes of problems occurring together rather than definite diagnosis of childhood disorders. The 99 questions are grouped into six dimensions or syndromes namely: (i) anxiety withdrawal scale, (ii) motor excess scale, (iii) attention problems scale, (iv) psychotic behavior scale, (v) socialized aggression, and (vi) conduct scale. The items are scored according to age-appropriate and sex-appropriate norms with a separate profile form. The response is made on a three-step response scale, scoring from 0 to 2, to give a final score suggesting normal, borderline, or clinical ranges. It was performed by well-trained psychologist using the Arabic standardized version.

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Conners’ Parent Rating Scale-Revised; long version 13

It is an 80-item questionnaire that scores parents’ report of their child’s behavior, aged 3–17 years, during the past month on a four-point response scoring, interpreted as being typical or atypical according to the five-point categorization. It was mainly used in assessment of the severity of attention-deficit hyperactivity disorder (ADHD), response to treatment, follow-up studies, and as Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnostic correspondence, especially in drawing symptoms profile.

Items are scored on 14 subscales of symptoms. We used the Arabic version, which was translated and validated to Arabic culture and used previously in many Arabic studies 15.

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CARS 14

The CARS is a 15-item scale used to identify children (>2 years) with autism and to distinguish mild to moderate from severe autism. Severe autism is diagnosed when the score is 36 or more. Items of the CARS are: relationship to people, imitation, emotional response, body use, object use, adapting to change, visual response, listening response, taste, smell and touch, tears or nervousness, verbal communication, nonverbal communication, activity level, level of intellectual response, and general impressions. We used the Arabic version, which was translated and validated to Arabic culture and used previously in many Arabic studies 16.

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Tools for cytogenetic analysis

After collection of 2–3 ml of venous blood from each patient under aseptic conditions into a sterile heparin-coated vacutaine and preparation of the culture in specific technique, the following was performed by a specialized and highly trained researcher to classify the patients into different genotypes:

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Conventional cytogenetic analysis by GTG banding technique

This technique is used to study the genome at the level of chromosomes at the metaphase stage (as the chromosome is most clearly defined) by the use of spindle fiber inhibitor (Colchicine). This is followed by hypotonic wash to swell the cells and spread the chromosomes, addition of fixative then slide making, and staining with Giemsa using trypsin to induce GTG banding, which can be clearly distinguished under the light microscope according to Verma and Babu 9.

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FISH technique

This technique relies on the unique ability of a portion of single-stranded DNA, known as a probe, to hybridize with its complementary target sequence wherever it is located in the genome. The probe is conjugated with a fluorescent label allowing it to be visualized under ultraviolet light. FISH technique was performed according to the modification by Pinkle et al. 10. When this probe set was hybridized to normal metaphase chromosomes, both chromosome one homologs are expected to have an aqua signal, single orange and green signals, which sometimes appeared as two distinct signals and sometimes appeared as one fused yellow signal. When the probe set was hybridized to a metaphase chromosome set having monosomy SNRPN, single chromosome 15 is expected to have a normal hybridization pattern, the other would be marked with an aqua signal, and the second orange signal would be absent.

Diagnostic criteria for PWS help in informing and raising detection of the syndrome. However, cytogenetic and molecular techniques are used to confirm the diagnosis. FISH, a cytogenetic technique that can identify and localize the presence or absence of specific DNA sequences on chromosomes, detects nearly all individuals with deletions in the chromosome 15 (q11–q13 region) 17,18. In addition, DNA methylation analysis detects methylation pattern characteristics with a sensitivity and specificity of nearly 100% 19.

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Statistical analysis

All data were collected, verified, revised, and then edited using a statistical package on a compatible computer. The data were then analyzed statistically using statistical package for social science version 13 (IBM Corporation, Chicago, Illinois, USA).

For descriptive statistics, number and percentage were calculated for categorical data. Inferential analyses were carried out for quantitative variables using the Student t-test for two independent groups. Qualitative data were analyzed using the Pearson χ2-test. The level of significance was taken at P value less than 0.05, otherwise was nonsignificant.

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Results

Of these patients, only 15 patients were included in our research. There were eight male patients and seven female patients, 53.3 and 46.7%, respectively. Their ages ranged between 6 and 13 years with a mean age of 8 years (±2.19 SD). Parental consanguinity was absent in nine patients (60%), remote in four (26.7%), and two of the patients’ parents were first cousins (13.3%). The education profiles of our patients were as follows: 10 did not go to schools (53.3%), three went to special needs facilities (26.7%), and three went to main stream schools (20%). The patients’ anthropometric measurements’ Z scores were as follows: the heights ranged between −3 and 0.00 with a mean of −1.05 (±0.932 SD), the weight lied between +3.5 and +15.00 with a mean of 7.00 (±3.34 SD), the head circumference was between −2.50 and +1.00 with a mean of −0.37 (±0.811 SD), whereas BMI ranged between 26.0 and 39.0 with a mean of 32.75 (±3.89 SD).

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Applying the Prader–Willi clinical diagnostic criteria

Application of this criteria to our patients showed that all patients had positive criteria from 8 to 12 with an average of 9.7 criteria. The frequency and percentage of positive findings in each of the major and minor criteria are shown in Table 2.

Table 2

Table 2

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The cytogenetic analysis results

The conventional cytogenetic analysis (by GTG banding technique) revealed no deletions. However, the FISH showed positive deletion in 10 patients (66.7% of the patients) as shown in Figs 1 and 2.

Figure 1

Figure 1

Figure 2

Figure 2

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Cognitive assessment through Wechsler Intelligence Scale for children showed the following results

One patient had borderline mentality (6.7%), three had mild mental retardation (MR) (20%), eight had moderate MR (53.3%), and three had severe MR (20%).

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The results of the CARS

Of our 15 patients, three had mild autistic features (20%) and one had significant autism (6.7%). In all, 73.3% were negative for autistic features.

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The results of the Revised Behavior Problem Checklist

Results showed the following: on socialized aggression scale, all our patients were negative (100%); on conduct scale, seven patients had mild conduct problems (46.7%), whereas four had significant problems (26.7%); on attention problem scale, all 15 patients had positive attention problems (100%); on anxiety withdrawal scale, four patients had mild anxiety withdrawal problem (26.7%) and four had significant problem (26.7%); on psychotic behavior scale, only one patient had psychotic behavior (6.7%); and on motor excess scale, four patients had mild motor excess (26.7%) and two had significant motor excess (13.3%).

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The results of Conners’ Parent Rating Scale

On oppositional subscale, six patients had mild oppositional traits (40%), whereas four had significant traits (26.7%); on cognitive problem subscale, all 15 patients had significant problem (100%); on hyperactivity subscale, three patients had mild hyperactivity (20%) and four had significant hyperactivity (26.7%); on anxious shy (anxiety) subscale, seven patients had mild symptoms (46.7%) and four had severe symptoms (26.7%); on perfectionism subscale, none of the patients had perfectionism; on social problem subscale, seven patients had mild social problems (46.7%) and four patients had significant social problems (26.7%); on psychosomatic subscale, four patients had mild symptoms (26.7%) and one patient had severe symptoms (6.7%); on liability subscale, six patients had mild liability (40%) and the other eight patients had significant liability (53.3%); on inattention subscale, two patients had mild inattention (13.3%) and the rest 13 patients had significant inattention (86.7%); on impulsivity subscale, nine patients had mild impulsivity (60%) and five had significant impulsivity (33.3%); on Conners’ ADHD severity index, seven patients had borderline result (46.7%) and four patients had significant possibility of a problems (26.7%); on DSM-IV inattention subscale, five patients were in the borderline clinical range (33.3%), whereas the other 10 were in the significant problem range (66.7); on DSM-IV Hyperactivity–Impulsivity subscale, three patients were in the borderline clinical range (20%) and four were in the significant problem range (26.7%); and on DSM-IV total score type, nine patients were in the borderline clinical range (60%), whereas three patients had significant possibility of a problem (33.3%).

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Evaluation of patients psychological profile with respect to their FISH results

On a trial to examine possible relationship between patients’ genetic profile and the associated cognitive and psychobehavioral problems, we did not find any statistically significant relationship between FISH-positive PWS patients (with 15q11–13 deletion) and FISH-negative PWS patients (without chromosome 15q11–13 deletion) and the diagnostic criteria or the intelligence quotient (IQ) of the patients in the two groups. However, there were significant differences in the psychosocial profiles elicited in CARS, Revised Behavior Problem Checklist and Conners’ parent rating scales with respect to patient FISH test results as following.

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On assessing autism by CARS

Three patients had mild autistic features and one had severe autism; all four patients were FISH negative, with significance at P value of 0.004 as in Table 3.

Table 3

Table 3

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On assessing patients’ behaviors by CBCL

On Anxiety Withdrawal subscale, the results showed significant correlation between nondeletion types of PWS and anxiety withdrawal behavior (AW). In the nondeletion group of five patients, two had mild anxiety withdrawal and three had severe withdrawal, whereas in the deletion group of 10 patients, seven were negative, two had mild AW, and only one had severe AW. The P value was 0.028 as shown in Fig. 3. On Motor Excess subscale, significant relationship was found between motor excess behavior (ME) and nondeletion types of PWS. Four of the five nondeletion patients had motor excess, whereas eight of the 10 deletion patients had no motor excess and only two had mild ME. The P value was 0.039 as shown in Fig. 4. On other subscales, there were nonsignificant differences.

Figure 3

Figure 3

Figure 4

Figure 4

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On assessing ADHD by Conners’ Parent Rating Scale

On oppositional subscale, the oppositional scores were positively related with nondeletion PWS patients. All five FISH-negative patients were oppositional: one had mild traits and four had significant traits, whereas five of the 10 FISH-positive patients were nonoppositional and five had mild traits (P=0.004). On hyperactivity subscale, significant relationship was found between hyperactivity and nondeletion patients. Four of the nondeletion patients had significant hyperactivity and one had mild hyperactivity, whereas eight of the 10 deletion patients had no hyperactivity and two had mild hyperactivity (P=0.002). On anxiety subscale, the anxiety scores were of significance in nondeletion patients; all five negative deletion patients had high anxiety scores, one had mild, and four had significant scores, whereas of the 10 deletion positive patients, four had no anxiety and six had mild anxiety (P=0.04). On social problems subscale, nondeletion patients were also found to have a higher inclination for social problems, as all five had social problems, two had mild, and three had significant problems, whereas only four of the positive deletion patients had mild problems and the rest had no social problems (P=0.011). On impulsivity subscale, all five FISH-negative patients were found to be impulsive, one had mild, and four had significant impulsivity, whereas in the 10 FISH-positive patients one had negative impulsivity, eight had mild, and only one had significant impulsivity. This implies the correlation between impulsivity and FISH-negative results with P value of 0.025. On ADHD severity index subscale, as a natural consequence of the previous correlations, the ADHD severity index of course showed a significant positive inclination toward the FISH-negative patients (P=0.011). On DSM-IV hyperactivity–impulsivity, the DSM-IV inattention score did not show any statistically significant difference; the DSM-IV hyperactivity–impulsivity score was obviously related again to the FISH-negative patients group with P value of 0.002. On DSM-IV total score, the total score was of course to follow as being directly related to the FISH-negative result, suggesting a strong correlation of ADHD symptoms with the nondeletion types of PWS (P=0.025) as shown in Table 4.

Table 4

Table 4

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Discussion

Because of slightly different behavioral profiles present in the different genotypes, because there are individual differences in the presence or absence of symptoms and the severity of symptoms 20, and because of the fact that little is known about the cause(s) of maladaptive behavior or other variables that are associated with the prevalence and severity of maladaptive behavior in individuals with PWS 21, we planned this study to evaluate psycho-socio-behavioral profile in a sample of Egyptian children with Prader–Willi Syndrome with respect to different modes of inheritance. Our results showed no sex preference as reported by others, as it comprised eight male patients and seven female patients 5. Patients’ education levels and socioeconomic class did not correlate significantly with patients’ major or minor diagnostic criteria and cognitive or behavioral findings, which is in agreement with studies describing PWS as complex neurodevelopmental disorder that affects ∼1 in 20 000 births with no distinguishing sex, race, or social status association 22. Positive parental consanguinity was detected in 40% of studied patients, which is similar to the percentage of consanguineous marriages published among Egyptian population 23. Patients’ anthropometric measurements were within the international ranges published in different studies on Prader–Willi Syndrome 24.

On applying FISH technique, 10 (66.7%) patients had the deletion type of syndrome. Several studies reported 60–70% deletion type among their patients 25,26. The FISH nondeleted patients may have one of the other etiological types of PWS, such as maternal UPD or imprinting defect.

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Analytical overview to the cognitive and psychosocial profile of the studied sample with respect to FISH results

Cognitive assessment through Wechsler Intelligence Scale for Children

In all, 73.3% of patients had mild to moderate MR. Lewis et al. 27 reported that mental retardation in most Prader–Willi syndrome patients is in the mild to moderate range 2. There are certain genes in the deleted chromosomal region in most patients with Prader–Willi syndrome (15q11–q13), including NIPA1, NIPA2, CYFIP1, and GCP5 genes. These genes are implicated in the lower intellectual ability observed in such patients because they have a great role in central nervous system development and/or function 28,29. However, irrespective of measured IQ, many of these individuals cannot perform at their predicted IQ score in everyday functioning because of untreated emotional and behavioral problems 30. PWS patients show a distinctive profile of strengths and weaknesses compared with individuals with intellectual disabilities 31. Expressive language disorder, poor auditory attention, restriction to sameness, food-related preoccupations and numerous maladaptive behaviors, and difficulty interpreting social information make it difficult for individuals with PWS to perform to their IQ potential 32.

However, some studies showed that deletion patients had generally lower IQ ranges than nondeletion patients 33. Others reported that the m-UPD PWS group has significantly higher verbal IQ scores than individuals with the deletion subtype of PWS 34. We could not find any significant difference in IQ range between deletion and nondeletion patients, neither in total nor in verbal and performance scores. This may be due to differences in the methodology and sample selection in different studies on one hand, and on the other hand because of small number of sample and rarity of large scale studies on this syndrome for which there were no enough comparative data, getting most of it from case studies.

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Analysis of sample psychiatric morbidities

In our study, 26% (four patients) of sample had autistic symptoms. With respect to their FISH results, all were FISH negative (80% of the FISH negative patients). Three of them had mild features and one had significant autism. None of the deletion type patients showed positive results on CARS using correlation coefficient test. Veltman et al.35 also suggested a strong correlation between autistic-like social behavior and UPD (one of the nondeletion types of PWS). In addition, study by Milner et al.36 indicated that studies on chromosome 15 abnormality have implicated overexpression of paternally imprinted genes in the 15q11–13 region in the etiology of autism. Others described it as genetic risk factor for autistic symptomatology 37,38. Interestingly, the types of repetitive behaviors seen in PWS are similar to those common in autism spectrum disorders 39.

On using Revised Behavioral Problem Checklist, our results showed that none of the patients showed significant socialized aggression. Studies to date have shown that the frequencies and severity of maladaptive behaviors are not uniform across the age groups. Steinhausen et al. 40 and Hartley et al. 41 found that individuals with PWS aged 20–29 years had significantly higher aggressive behavior scores than those aged 12–19 and 30–45 years. The mean age of our sample was 8 years, where no marked aggression was reported. In all, 73.4% of the patients had conduct problems with no significant difference between deletion and nondeletion type. Similarly, another study reported that majority of their patients scored in the pathologic range for social and attention problems, delinquent problems, somatic complaints, and thought problems. In disagreement with our result, their patients showed that marked aggressive behavior and genotypes of the children did not predict cognitive or behavioral profile 30. Different sampling and inclusion and exclusion criteria can result in differences, especially that their patients had their mean IQ as 73.7±8.9, which was 1 SD below normal range 30.

Approximately one-third of the patients (33.4%) had psychosomatic manifestations with different severities unrelated to their mode of inheritance. Patient’s low mental and social abilities and their helplessness in facing everyday challenges can contribute in the development of this symptom. This was in agreement with reports which found higher levels of psychosomatic complaints in patients with Prader–Willi syndrome than in other patients with mental subnormality 30.

Approximately half of the patients (53.4%) showed anxiety withdrawal problem equally divided between mild and significant severity. A theory to explain the high occurrence of anxiety in those children was mentioned in a study stating that most children with PWS, young and old, have strong need for structure and consistency and they often exhibit higher level anxiety when there is a change or perceived change. Those children may worry about how a change impacts food, such as when, what, where, and how much 42. Higher scores for anxiety withdrawal behavior were related to nondeletion PWS patients (100% of patients) more than the nondeletion type patients (20% of patients), with significant P value of 0.028.

One patient (6.7%) had psychotic manifestations and had a FISH-negative result (nondeletion). This is in agreement with a study that suggested the presence of high risk of psychotic behavior in patients with PWS, especially those with maternal UPD, due to excessive maternal gene expression that produces overly mentalistic cognition and behavior, which renders patients more prone to psychotic spectrum disorders 3.

All patients had attention problems and cognitive impairment ranging from mild to significant, with no difference between deletion and nondeletion type which coincides with some studies and contradicts with others reporting more problem in deletion type 43,44. Moreover, 40% of patients had motor excess: 80% of them were nondeletion patients and just 20% were deletion type and mostly presented in mild form, suggesting some relationship between motor excess behavior and nondeletion, with P value of 0.039. This was not similar to a study that reported similar high rates of ADHD symptoms and maladaptive conduct problems but with higher severity in individuals with paternal deletion than m-UPD 43.

Conner Parent Rating Scale results confirmed most of the CBCL scores. In addition, they reflected high incidence of ADHD in our patients. On DSM-IV total score, 90% from the deletion type and 100% from the nondeletion type had significant scores. However, the DSM-IV inattention subscale showed high inattention score in all patients, enough to diagnose them as ADHD inattention type; it did not show any statistically significant difference between the two genotypes. DSM-IV hyperactivity–impulsivity score obviously showed significant difference in favor of the FISH-negative patients group. Higher severity and incidence ratio were significantly associated with the nondeletion type as reflected in all following subscales; P values were 0.025, 0.004, 0.002, 0.04, 0.011, and 0.025 for Total, Oppositional, Hyperactivity, Anxiety, Social problems, and Impulsivity scores, respectively. In addition to what was mentioned above regarding association of PWS especially the nondeletion type with inattention, hyperactivity, anxiety, social and behavioral problems 43,44, studies by Scheimann 45 and Skokauskas et al.46 stated that children with PWS had more severe somatic, social, and thought problems, attention deficit hyperactivity, and were more withdrawal depressed in comparison with controls.

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Conclusion

From the above results, we can conclude that cognitive and psychological challenges are a fixed part of the PWS patients’ profiles. Some differences have been found within different genotypes of our study group, such as the higher prevalence of autistic features, hyperactivity, anxiety, and social and behavioral problems within the nondeletion group, but nevertheless they all complained of some element of cognitive delay and many psychosocial difficulties. Interestingly, there were no statistically significant differences neither in the clinical diagnostic criteria nor in the IQ of the patients in the two genotypes; there were obvious differences in the psychosocial profiles elicited in Conner Parent Rating Scales and CBCL. These results should be seen in the light of the later-mentioned limitations and suggested recommendations.

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Limitations and points of strength in the study

To the best of our knowledge, this study is considered the first study conducted to assess cognitive and psychosocial abilities and deviations in Egyptian patients with PWS. Our aim was to shed some light on this neglected and seldom diagnosed syndrome through studying related parameters and profiles with respect to patient’s mode of inheritance. This may help in the prevention of missing these patients being considered just simple obesity at times. Until now, there is no universal treatment strategy for approaching psychobehavioral problems in PWS patients, which primarily needs detailed neuropsychiatric assessment.

During this study, we faced difficulties in finding the patients and confirming the diagnosis; thus sample size may be not exactly adequate to draw firm conclusions and to draw sufficient evidence, but it could be considered as a step on the way in studying such relatively neglected genetic syndromes. In addition, the sample was limited to the clinic-referred patients that disables us to generalize the findings on the whole PWS population. Moreover, this syndrome is very rarely properly diagnosed, which may limit our patients to severe cases who had striking enough signs to prompt referral to a genetics specialist. This study is cross-sectional descriptive study, which limits assessment to certain age range. Assessing PWS patients through different life stages could have resulted in different conclusions because of changing psychobehavioral profile with age as reported in multiples studies. In addition, absence of control group especially to other patient with other intellectual disabilities could have added important conclusions. We could not assess OCD symptoms in our patients in detail, as we did not use obsessive–compulsive subscale of CBCL or other validated scales, and hence missed proper assessment of one of the most frequent behavioral problems in these patients. More detailed genetic analysis could have helped in giving a more detailed picture, especially regarding different deletion subtypes.

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Recommendations

Maladaptive behaviors and cognitive impairment in PWS patients have important implications on their childhood, adolescence, and adulthood. It can affect long-term functioning of an individual and their families. Understanding difficulties underlying the maladaptive behavior will allow for better management of the syndrome. Therefore, it is important, not only to manage and treat the most striking features of PWS, such as hyperphagia and weight-related issues first, but also to be aware of the secondary behavioral and cognitive implications through proper assessment protocol and proper management plan. Moreover, more studies are needed in this area especially in Egypt and the Arab countries bypassing methodology and sampling problems to be more able to draw firm conclusions and accordingly set for clear management strategies.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

cognitive; genotype; Prader–Willi syndrome; psychosocial profile

© 2014 Institute of Psychiatry, Ain Shams University