Growth hormone, gender and face shape in prader–willi syndrome

Abstract

Prader-Willi syndrome is a neurodevelopmental disorder resulting from the absence of expression of paternally expressed gene(s) in a highly imprinted region of chromosome 15q11-13. The physical phenotype includes evidence of growth retardation due to relative growth hormone deficiency, small hands and feet, a failure of normal secondary sexual development, and a facial appearance including narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal root, and thin upper vermilion with downturned corners of the mouth. Anecdotally, the face of individuals with PWS receiving hGH treatment is said to "normalize." We used dense surface modelling and shape signature techniques to analyze 3D photogrammetric images of the faces of 72 affected and 388 unaffected individuals. We confirmed that adults with Prader-Willi syndrome who had never received human growth supplementation displayed known characteristic facial features. Facial growth was significantly reduced in these adults, especially in males. We demonstrated that following human growth hormone (hGH) supplementation, vertical facial growth of affected individuals falls within the normal range. However, lateral and periorbital face shape and nose shape differences in affected children who have received hGH therapy remain sufficiently strong to be significantly discriminating in comparisons with age-sex matched, unaffected individuals. Finally, we produced evidence that age at initiation and length of treatment with hGH do not appear to play a role in normalization or in consistent alteration of the face shape of affected individuals. This is the first study to provide objective shape analysis of craniofacial effects of hGH therapy in Prader-Willi syndrome.

Characterization of facial phenotypes of children with congenital hypopituitarism and their parents: A matched case‐control study

“…However, lateral and periorbital face shape and nose shape in affected children who have received GH therapy remain significantly different in comparison with age-sex matched, unaffected individuals. It was also shown, in agreement with the findings of our study, that age at initiation and length of treatment with GH do not play a role in normalization or in consistent alteration of the face shape of affected individuals [De Souza et al, 2013].…”

Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf–Hirschhorn Syndrome

“…Patient 1's vertical face length was normalized, perhaps by a year of hGH treatment, as similar findings have been observed in Prader-Willi syndrome patients treated with hGH. 25 The only other significant difference from controls was in forward displacement of the inner and outer canthi, shown in the anterior-posterior signature. The bilateral red regions adjacent to the lower lip in the anteriorposterior comparison are likely due to a non-neutral pose.…”

“…These findings were somewhat unexpected based on deletion size comparison. Evidence from a recent study of patients with Prader-Willi syndrome suggests that dysmorphic features persist even if face length is normalized by growth hormone therapy, 25 arguing against a misclassification of patient 1.…”

Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development

“…In contrast, soft tissue growth and morphology has been extensively studied in normal and abnormal development, as measurements can be easily obtained through anthropometrics (Farkas et al, 1992; Tutkuviene et al, 2015) or surface modelling using 3D imaging (De Souza et al, 2013; Koudelová et al, 2015; Suttie et al, 2013). Craniofacial shape and variation can be quantified using morphometric analysis (MA), which has been widely used to study heterogeneity in soft tissues of the face, classify non-genetic diseases, demonstrate normal growth and facial asymmetry, and link gene expression to facial phenotype (De Souza et al, 2013; Hammond et al, 2003; Hopman et al, 2014). Although quantitative analysis of the facial skeletal tissues for preoperative planning has been undertaken in TCS, this only used cephalometric analysis or focused on mild dysmorphism (Chong et al, 2008; Nikkhah et al, 2013).…”