Growth Trajectories in Genetic Subtypes of Prader–Willi Syndrome

Abstract

<jats:p>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.</jats:p>

Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader–Willi Syndrome

“…There is also little data for anthropometric characteristics before rhGH treatment in relation to the molecular type of diagnosis. The latest research does not give concordant results regarding overall anthropometric differences between the genetic subtypes [ 34 , 35 , 36 , 37 ]. In the study by Butler et al in 2019, regarding both paediatric and adult patients, with only part of them treated with rhGH, there was no difference in body mass index (BMI) identified, based on the genetic subtype [ 34 ].…”

“…In the recently published paper by Shepherd et al in 2020, describing paediatric population, detailed information regarding rhGH treatment was not reported and no difference in height was found for males in both PWS subtypes (DEL 15 vs. non-DEL 15), with decreased height in females with non-DEL 15 for older ages. Weight and BMI were higher in the DEL 15 group, which suggests that these patients are more prone to obesity [ 35 ]. These results correspond with the findings by Mahmoud and Leonenko et al in a multicentre study of a large cohort of 355 patients, published this year [ 36 ].…”

Long‐term weight control in adults with Prader‐Willi syndrome living in residential hostels

“…Shepherd found that the deletion subtype was associated with a greater weight and BMI compared with non‐deletions (Shepherd et al, 2020). Also, Dudley reported lower BMI values in the UPD group than those with deletions (Dudley et al, 2008).…”

Clinical response to biologicals for severe asthma: any relevance for sex in different age ranges?

“…For the first set of analyses, three random intercept LMMs were fitted for each of the outcomes and for each sex subgroup separately, including measurement time as a fixed factor variable (with levels set up to 1, 3, 6 and 12 months after start of therapy). These models allowed for a direct interpretation of fitted model parameters as representing the average longitudinal growth/decline of the lung function outcome over the follow-up time, distinctly for men and women [ 18 ].…”