Facial phenotype of Prader-Willi syndrome becomes more normal with early growth hormone treatment

Suzanne B. Cassidy¹, Ellen Simpson¹, Shauna Heeger²

¹Division of Human Genetics, Department of Pediatrics, University of California, Irvine, 101 The City Drive, Bldg 2, Orange, CA 92868, (714) 456-8520,  and  ²Case Western Reserve University 

The classical physical appearance of Prader-Willi syndrome (PWS) is most notable for characteristic facial features (narrow bifrontal diameter, almond-shaped and sometimes upslanting palpebral fissures, downturned corners of the mouth), short stature, central obesity, small hands and feet, genu valgus, and decreased muscle mass causing straight ulnar borders and straight calf borders. In recent years, the short stature, as well as altered body composition, has been attributed to growth hormone deficiency, since they improve with replacement therapy.  Many newly diagnosed individuals are being treated from the time of diagnosis, which is often infancy.  Observation of treated patients has demonstrated significant impact on phenotype.

Published reports of double-blind crossover studies of recombinant human growth hormone (rhGH) treatment in PWS have demonstrated dramatic increase in growth rate (especially in the first year of treatment) and a variety of other effects, including: 1) improved body composition  (higher muscle mass, lower fat mass), 2) improved weight management; 3) increased energy and physical activity; 4) improved strength, agility and endurance; and 5) increased respiratory muscle forces. No study has specifically addressed facial appearance.

We have been conducting an ongoing multi-system detailed standardized phenotypic evaluation of individuals with PWS over the past few years in a study designed to make genotype-phenotype comparison.  However, given the recent shift to rhGH treatment, recently enrolled patients with rhGH replacement can be compared phenotypically to earlier enrolled patients, who were not rhGH treated. Such comparisons, as well as review of patients followed in a multi-disciplinary PWS management clinic and of studies by others, indicate a number of effects on phenotype. These comparisons primarily document the normalization of facial appearance, as well as improvement towards normal body habitus.  Although such comparisons are difficult to make quantitative or objective, this presentation will show, using multiple examples, the differences in facial appearance between those who have, and those who have not, been treated with rhGH. Body habitus will also be compared. Such photos show impressive differences, with individuals who are rhGH treated over a period of years lacking the typical facial gestalt of PWS.

This study will demonstrate that normalization of facial and body appearance can be added to the benefits of growth hormone therapy in PWS.

June 2004