The transition between the phenotypes of Prader–Willi syndrome during infancy and early childhood

Abstract

In the half-century since the description of Prader–Willi syndrome (PWS) there has been a considerable body of work devoted to delineation of the genetic mechanisms behind the development of PWS, and to improving our understanding of the physical manifestations, and behavioural and cognitive effects of the disorder. Generally, infants with PWS cannot suck properly and many are gavage-fed. They often fail to thrive, although Eiholzer et al. reported that even underweight infants with PWS have abnormally high body-fat measures. An interesting facet of PWS is hyperphagia which is almost universal after the age of 3 years. Earlier thought to be a manifestation of extreme hunger, hyperphagia in PWS is now considered to reflect a disruption of the normal satiety signal. In fact, some researchers have suggested that PWS is a starvation syndrome, whereby the body responds to the lack of satiety signal as if starving, with the result that the person continues to eat whenever food is available. Treatment with growth hormone has been shown to improve linear growth and to decrease fat-mass to muscle-mass ratios, but it appears to have little, if any, effect on the abnormal eating behaviours of people with PWS. There has been little research into the transition period between the early childhood phenotype of failure to thrive and the older, hyperphagic phenotype. A study by Butler et al. sheds light on this under-investigated stage of the disorder. Overall, they found considerable variation in the age at which children first exhibited an increased interest in food, and significantly fewer children displayed the full food obsession pattern of behaviour than would be expected from other reports. However, body mass index (BMI) standard deviation scores tended to increase around 30 months of age, before any notable increase in the characteristic eating behaviour as reported by many parents, thus supporting the suggestion that there are in fact three stages involved in the development of PWS: failure to thrive in infancy, increased BMI or obesity in early childhood, and hyperphagia leading to greater obesity in later childhood and adulthood. One limitation faced by Butler et al. was that just over one-third of participants had received growth hormone therapy for varying lengths of time, with insufficient numbers to attain statistical significance. A larger-scale longitudinal study could usefully explore the use of growth hormone in infancy and clarify the apparent delay in the transition between phenotypic stages resulting from the treatment. An important advance is the development of an Eating Code specifically for use with younger age groups. A Food-Related Problems Questionnaire already exists for older people with PWS, and there appear to be many similarities between the two instruments. However, the inclusion of questions relating to the need for and use of food control measures to determine the Eating Codes appears to be unique to this study and promises to be a