Growth Trajectories in Genetic Subtypes of Prader-Willi Syndrome.

Daisy A Shepherd,Margarita Moreno-Betancur,David E Godler,Angela Guzys,David J Amor,Niels Vos,Susan M Reid

doi:10.3390/genes11070736

Abstract

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.

Highlights

Prader–Willi syndrome (PWS) is a rare multisystem disorder caused by the loss of transcription of several genes and RNA transcripts on the paternally inherited copy of chromosome 15 [1]
From the Victorian Prader–Willi Syndrome Register (VPWSR), we identified a retrospective cohort of individuals with a known molecular mechanism and at least one recorded height and weight measurement
For females with PWS, the size of difference in mean weight and mean Body Mass Index (BMI) was more pronounced over the age range of 5 to 15 years, while the difference in mean weight for males was more pronounced over the age of 10 years and fairly consistent over age for BMI

Summary

Introduction

Prader–Willi syndrome (PWS) is a rare multisystem disorder caused by the loss of transcription of several genes and RNA transcripts on the paternally inherited copy of chromosome 15 [1]. Key early clinical features are infantile hypotonia and poor sucking with failure to thrive, followed in childhood by food seeking and hyperphagia that may lead to morbid obesity [2,3] and early mortality [4] if not externally controlled. Short stature and small hands and feet. In approximately 65% of cases, PWS is caused by a deletion which removes either 5.0 Mb (class I deletion) or 5.9 Mb (class II deletion) of the paternal chromosome within 15q11-13 [5,6]. There is no alteration to the copy number at

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