Growth hormone and Prader-Willi syndrome: experience and perspective

The initial report of Prader-Willi syndrome (PWS), published in 1956, described five major morbidities: short stature, hypotonia, obesity, hypogonadism, and cognitive delay. The clinical definition of PWS was fine-tuned over the next 3 decades; reported association with abnormalities in chromosome 15q in the 1980s led to the genetic definition in the 1990s. Human growth hormone (GH) was first purified in the 1950s, followed by increased therapeutic use of preparations purified from human pituitaries, which were emergently replaced by recombinant DNA-produced GH in 1985. Coincident developments in both fields led to trials of GH treatment for PWS and regulatory approval of GH treatment for PWS in 2000. As the only therapeutic agent with worldwide labeling for PWS, GH has shown efficacy for growth and hypotonia. Potential benefits for cognitive function and obesity have also been suggested, particularly with early treatment. A warning added in 2002 to the GH label for the PWS indication regarding use in severe obesity and severe respiratory impairment does not appear to be fully evidence-based; few other adverse effects have been observed. Delayed diagnosis and treatment of PWS continues to be a significant problem. The inclusion of PWS in newborn screening programs, a current area of research, would address the issue of late diagnosis, facilitating earlier initiation of GH treatment. Initial steps toward genetic therapy provide hope for a more complete medical treatment for this condition.