Executive functioning in adolescents and adults with Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation. The two principal causes of SRS are loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Knowledge of the neuropsychological profile of SRS remains sparse and incomplete even if several difficulties related to attention and learning have been reported both in the literature and by patients with SRS. These difficulties could be the result of troubles in different cognitive domains, but also of executive dysfunction. Nevertheless, executive functioning has never been investigated, even though executive functions play an essential role in psychological development, and are extensively involved in daily life. The present study explored the executive functioning of individuals with SRS due to UPD(7)mat or 11p15 LOM. A battery of executive tasks assessing cognitive flexibility, inhibitory control, and working memory, together with a task assessing sustained attention, was administered to 19 individuals with SRS (13-39 years) and 19 healthy controls. The Behavior Rating Inventory of Executive Function was also completed by the participants' families. The results showed that participants with SRS had similar performance (z-scores) to our controls, in a context of normal intellectual efficiency. Group comparisons with Bayesian statistics showed a single difference between the 11p15 LOM and control groups: the completion time for part A of the Trail Making Test appeared to be longer in the 11p15 LOM group than in the control group. However, at the clinical level, several participants with SRS had clinically significant scores on various measures of EFs. Thus, the cognitive phenotype of SRS did not appear to be characterized by executive dysfunction, but individuals with SRS could be at high risk of developing executive dysfunction or attention-deficit/hyperactivity disorder. These results provide new insights into the neuropsychological profile of individuals with SRS.

Quality of life and mental health of adolescents and adults with Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation. Despite normal intellectual functioning, psychosocial and behavioral difficulties have been observed in this syndrome. However, few studies have dealt with these aspects, even though this could enhance the current understanding of the SRS and, more importantly, improve the management of potential psychosocial problems. Given the sparse literature, this cross-sectional study aimed to establish the psychosocial and behavioral profile of individuals with SRS. To this end, we assessed the quality of life (World Health Organization Quality of Life Questionnaire-Short Form), self-esteem (Coopersmith's Self-Esteem Inventory), anxiety (Spielberger's State-Trait Anxiety Inventory), and behavioral and emotional problems (Child Behavior Checklist and Adult Behavior Checklist) in a sample of 19 adolescents and adults with SRS and 18 without SRS (controls). We also analyzed clinical features, molecular genetic diagnosis, and past or current treatments of participants with SRS. Based on prior studies, we expected to observe psychological and behavioral difficulties in our clinical population. We also expected these difficulties, shared by both adolescents and adults with SRS, to be associated with factors such as height, genetics, or treatment. Overall, our results showed that participants with SRS had similar performances to those of controls, despite high interindividual variability among the adults with SRS. For example, while adults with SRS had a similar mean total self-esteem score to control participants, 45% of the adults with SRS still had very low self-esteem. In addition, adolescents and adults with SRS did not necessarily have the same difficulties. Social and behavioral problems appeared to be more common in adolescents with upd(7)mat while in adults, difficulties were not associated with either height, weight, NH-CSS score, or GH treatment but did appear to be associated with GnRHa treatment. Indeed, low self-esteem was associated with GnRHa treatment. Overall, this study shows that early intervention and multidisciplinary care right up to adulthood, including psychological support, are needed for this population, regardless of the molecular abnormality responsible for SRS, to cope with potential psychosocial problems.

Intellectual functioning in Silver-Russell syndrome: First study in adults.

Silver-Russell syndrome (SRS) is a rare genetic disorder (estimated incidence 1/30,000 to 100,000 live births). So far, only a few studies have focused on the cognitive profile of individuals with SRS, and these were conducted some time ago, concentrated on pediatric cohorts, and included patients who had been diagnosed using a variety of clinical diagnostic systems. There has yet to be any research on the intellectual functioning of adults with SRS. This study sought to establish the intelligence, strengths and weaknesses within intellectual profile of adults with SRS, compared with normative data. Ten individuals with 11p15 epimutation aged 18-39 years completed the Wechsler Adult Intelligence Scale-Fourth Edition. Measures of interest included participants' intelligence (Full Scale Intelligence Quotient [FSIQ]) and four domains of cognitive functioning: verbal comprehension, perceptual reasoning, working memory and processing speed. Discrepancy scores were calculated, and descriptive statistical and linear correlations were used to investigate factors associated with IQ outcome. Clinical and medical information such as rehabilitation, and perceived difficulties in daily life were collected by interviews and questionnaires. Results showed that the mean FSIQ score was in the average range (M = 95.40, SD = 18.55) and they performed best on verbal comprehension. Frequent daily difficulties were reported by patients and/or their families: learning disabilities and low self-esteem were perceived by 60% of adults. Early intervention and multidisciplinary care from childhood to adulthood are important in SRS for care potential medical, cognitive and psychosocial problems. This is the first study to document the intellectual functioning of adults with SRS.