Growth Trajectories in Genetic Subtypes of Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a rare disorder caused by the loss of expression of genes on the paternal copy of chromosome 15q11-13. The main molecular subtypes of PWS are the deletion of 15q11-13 and non-deletion, and differences in neurobehavioral phenotype are recognized between the subtypes. This study aimed to investigate growth trajectories in PWS and associations between PWS subtype (deletion vs. non-deletion) and height, weight and body mass index (BMI). Growth data were available for 125 individuals with PWS (63 males, 62 females), of which 72 (57.6%) had the deletion subtype. There was a median of 28 observations per individual (range 2-85), producing 3565 data points distributed from birth to 18 years of age. Linear mixed models with cubic splines, subject-specific random effects and an autoregressive correlation structure were used to model the longitudinal growth data whilst accounting for the nature of repeated measures. Height was similar for males in both PWS subtypes, with non-deletion females being shorter than deletion females for older ages. Weight and BMI were estimated to be higher in the deletion subtype compared to the non-deletion subtype, with the size of difference increasing with advancing age for weight. These results suggest that individuals with deletion PWS are more prone to obesity.