Influence of molecular classes and growth hormone treatment on growth and dysmorphology in Prader‐Willi syndrome: A multicenter study

Abstract

Prader‐Willi syndrome (PWS) is a complex genetic disorder with three molecular classes but clinical ascertainment is based on distinctive features. The prevalence of dysmorphic features was studied in 355 PWS participants (61% deletion, 36% maternal disomy [UPD], and 3% imprinting defects) from the National Institute of Health PWS Rare Diseases Clinical Research Network. The effect of growth hormone (GH) treatment on growth and dysmorphic features was compared. Among participants, upslanting palpebral fissures were seen in 23%; strabismus in 42%; abnormal dentition in 32%; small hands in 63% and small feet in 70%; hypopigmentation in 30%; striae in 32% and skin picking in 26%. Compared to those with UPD, participants with deletions were found to be heavier (p = 0.002), had smaller head circumference (HC) (p = 0.009), higher incidence of a flat occiput (p = 0.005); low‐anterior hairline (p = 0.04); abnormal dentition (p = 0.009); abdominal striae (p = 0.045), nail abnormalities (p = 0.050), and fair‐haired (p < 0.001). Participants in both genetic groups receiving GH were taller (p = 0.005), had larger HCs (p = 0.005), and longer hands (p = 0.049). This study suggested that PWS genetic subtypes and GH treatment can influence growth and dysmorphic features that may impact clinical diagnosis of PWS, such as stature, head shape and appearance of the eyes, nose, and genitalia.

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

“…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 ]. However, the authors of the above studies did not analyse the characteristics of patients with PWS with a different molecular diagnosis at the start of rhGH therapy.…”

“…It may be also speculated that the clinical, mainly dysmorphic features of PWS, other than short stature or higher BMI, are more relevant in the children with DEL 15. The DEL 15 phenotype has been described as a classic PWS phenotype that may therefore lead to the earlier diagnosis and start of the therapy [ 28 , 36 ]. The evident difference between the birth length SDS and height SDS before the start of the treatment in our research, independent of the genetic subtype, may indicate that there is a significant decrease in postnatal growth in children with PWS, regardless the specific molecular diagnosis.…”

“…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 ].…”

Incidence of strabismus, strabismus surgeries, and other vision conditions in Prader-Willi syndrome: data from the Global Prader-Willi Syndrome Registry

“…Previous reports of strabismus among individuals with PWS range from 28 to 95 % [ 11 ]. Most recently, a clinical study of the effect of growth hormone therapy on 355 PWS participants reported a strabismus prevalence of 42 %, which is line with the results reported here [ 17 ]. That study also showed a statistically higher prevalence of strabismus in individual with PWS by UPD versus those with the deletion subtype (53 % vs. 39 %) [ 17 ].…”

“…Most recently, a clinical study of the effect of growth hormone therapy on 355 PWS participants reported a strabismus prevalence of 42 %, which is line with the results reported here [ 17 ]. That study also showed a statistically higher prevalence of strabismus in individual with PWS by UPD versus those with the deletion subtype (53 % vs. 39 %) [ 17 ]. The current study of data from the Global PWS Registry, with almost 3 times the number of subjects, did not confirm this suggested difference in prevalence of strabismus by genetic subtype.…”