Rehabilitation issues for children with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a complex neurodevelopmental disorder first described in 1956 [1]. Almost three decades later, PWS was the first recognized microdeletion syndrome identified in humans (previously microdeletion was found only in plants) [2], [3]. PWS is caused by an error in genetic imprinting, specifically, in the region of 15q11–q13 [4–6]. A paternal interstitial deletion is found in approximately 70% of individuals with PWS, approximately 25% have maternal disomy and the remaining 5% have microdeletions, epimutations or chromosome 15 translocations [5–8]. Two subtypes of deletions have been suggested. Type I involves longer deletions and Type II shorter deletions, relative to the breakpoints on the gene [7]. However, additional research is required to determine potential behavioural or developmental differences between these subtypes. The male to female ratio is about equal, and PWS is not associated with any particular ethnic group, geographic region or socioeconomic class [9–11]. Prevalence estimates range between 1 in every 8000 to 1 in every 29,000 live births [10–12]. Perhaps, because of its relatively low prevalence, PWS has received relatively little attention from rehabilitation researchers and professionals. The aim of this editorial is to raise awareness of PWS by providing a brief overview of the associated developmental and behavioural characteristics. We hope that this overview will stimulate interest and research into the rehabilitation of children with this syndrome. To stimulate research, we offer suggestions for areas in need of empirical investigation.

In 1956, Prader, Labhart and Willi described five males and four females who, as infants, experienced hypotonia, weak or absent reflexes, a general lack of movement and an inability to cry or suck. Around 2 years of age, movement and hypotonia had improved, but obesity, growth deficiency (e.g. short stature) and intellectual disability emerged [1], [11]. Currently, diagnosis of PWS is made using consensus clinical criteria and is confirmed via genetic testing [13]. PWS is a multiphase disorder and can be classified within three different phases (i.e. Hyptonic Phase, Hyperphagic Phase and Adolescene/Adult Phase) with developmental and behavioural concerns emphasized within each stage [13].

The Hypotonic Phase (prenatal to infancy) is characterized by reduced foetal activity, low weight, weak muscle tone, hypogonadism, cryptorchidism, respiratory difficulty and general delay in developmental milestones. Treatment during this phase is likely to be focused on feeding difficulties and physical therapy [13–15]. The Hyperphagic Phase (childhood) is characterized predominately by the emergence of maladaptive behaviours including tantrums and aggression related to obtaining food, self-injurious behaviour (skin-picking) and insistence on routines. Obesity, short stature and cognitive dysfunction are also likely to become apparent. Education and treatment in this phase may include weight management, behavioural therapy, social skills training, speech therapy, medication and physical/occupational therapy. The Adolescents to Adulthood Phase is characterized by infertility, delayed sexual development, Scoliosis and glucose intolerance or diabetes. Life expectancy does not often exceed 60 years with the leading causes of death being cardio-respiratory failure [10], [12], [13].

Research regarding the medical treatment of PWS is extremely sparse. One recent approach involves the use of growth hormones (GH). Because individuals with PWS have a body pattern similar to individuals with GH deficiency, GH therapy has been evaluated as one potential treatment for characteristics associated with PWS [16]. Although improvements in height, lean body mass, muscle strength and agility have been reported, GH therapy may also be associated with the increased risk of obstructive sleep apnea (OSA) [17]. It has been suggested that OSA resulting from GH therapy may be one factor contributing to sudden death in children with PWS [17].

Treatment studies concerning the range of behavioural and psychological issues commonly associated with PWS are also lacking. For example, the prevalence of chronic skin-picking in samples of individuals with PWS has been found to be as high as 75–85% [13], [18]; however, no published research has investigated a behavioural treatment for skin-picking with this population. Other behaviour concerns commonly associated with PWS in which intervention research is warranted include verbal perseveration, stubbornness, obsessive food seeking and overeating, hoarding, tantrums, disobedience, impulsivity and excessive sleep [13], [19]. Although intervention research targeting some of these behavioural topographies (e.g. tantrums) does exist within populations of individuals with other types of developmental disabilities, the unique developmental trajectory and the tendency for obsessive or ritualistic behaviours in individuals with PWS suggest additional intervention research focusing on this population is warranted.

Another avenue for research on PWS centres on the investigation of gene-environment interactions (GxE) [20]. Although, PWS is associated with highly specific topographies of challenging behaviour, little is known about the developmental process that leads to the initial emergence and subsequent maintenance of these behaviours in the syndrome. It seems likely that GxE may play an important role in this process [20]. For example, people with PWS are known to have an altered satiety response to food, which may in turn place such individuals at a heightened probability of displaying challenging behaviours that are reinforced by access to food [21]. Further empirical investigation of such relations should be a priority for researchers as they hold important implications for the early detection, intervention and prevention of challenging behaviour in PWS.

Thanks to previous research, much is known regarding the nature and developmental trajectory of PWS. This knowledge will be indispensable in efforts to treat PWS. Due to the advanced knowledge of the PWS phenotype, it seems that further research of the role of GxE in the syndrome could serve as a springboard from which to begin to investigate such relations across other neurodevelopmental disorders.