Robustness of Distinctive Facial Features in Prader-Willi Syndrome: A Stereophotogrammetric Analysis and Association with Clinical and Biochemical Markers in Adult Individuals

SIMPLE SUMMARY: Prader-Willi syndrome (PWS) is a rare genetically determined neurodevelopmental disorder usually associated with a peculiar facial appearance. There is poor information concerning the relationships between the facial dysmorphism in PWS and other manifestations of the disease and its treatment. This exploratory study aimed to investigate this aspect, since this knowledge might aid in both diagnosis and monitoring of the disease. Three-dimensional facial images of fifteen Caucasian adult individuals with PWS were acquired through stereophotogrammetry; linear distances and angles were then calculated and compared with those of groups of healthy subjects matched for sex and age, obtained using the same noninvasive procedure. Individuals with PWS were evaluated for endocrine/metabolic dysfunction and nocturnal respiratory function, and their associations with facial features were tested. Some facial characteristics did not show any associations with other manifestations of PWS; therefore, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Conversely, other facial characteristics showed relationships with clinical and biochemical markers of PWS, suggesting their potentially useful role in the clinical monitoring and management of the disease. Further studies are needed to confirm these findings. ABSTRACT: Background: Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder associated to a complex neurodevelopmental phenotype and a distinctive facial appearance. The study investigated the relationships between the quantitative facial dysmorphism in PWS and clinical and biochemical markers of the disease and its treatment. Methods: Facial images of 15 Caucasian adult individuals with PWS (8 males, 42 ± 5 years; 7 females, 37 ± 8 years; BMI 38.87 ± 8.92 kg/m(2)) were acquired through stereophotogrammetry. From the 3D coordinates of 38 landmarks, linear distances and angles were calculated; they were expressed as z-score values by referring to 403 healthy subjects matched for age and sex and compared by Student’s t-test with Bonferroni correction for multiple testing. Patients underwent auxological and biochemical assessment of endocrine/metabolic dysfunction and nocturnal respiratory function. An exploratory correlation analysis was performed to investigate their associations with the facial phenotype; uncorrected p-values were used. Results and Conclusions: Individuals with PWS showed decreased bifrontal diameter, facial depths, palpebral fissures, mandibular ramus length, lower vermillion height, and modified relative position of exocanthia and nasion. Since these characteristics did not show any associations with clinical and biochemical markers of PWS, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Individuals with PWS showed also a larger mandibular width with smaller gonial angles, thinner upper vermillion, greater inclination of the orbit relative to the Frankfurt plane, and a smaller angle of the auricles versus the facial midplane. Relationships between these facial anthropometric features and body composition, glucidic metabolism indexes, nocturnal hypoxemia episodes, or duration of GH treatment were found, suggesting their potentially useful role in the clinical monitoring and management of the disease. However, they need to be confirmed by subsequent dedicated studies.