Prader-Willi Syndrome : Adrnarche, gonadal function, cognition, psychosocial aspects and effects of growth hormone treatment in children

The first patient with Prader-Willi syndrome (PWS), described in 1887 by Langdon-Down1 (Figure 1), was an adolescent girl with mental impairment, short stature, hypogonadism, and obesity. The first official group of patients with PWS was described by endocrinologists Prader, Labhart, and Willi in 19562. They described an unusual pattern of abnormalities, including neonatal hypotonia resulting in feeding problems in infancy, cryptorchidism, short stature and retarded bone age, small hands and feet, delayed developmental milestones, characteristic faces, cognitive impairment, onset of gross obesity in early childhood due to insatiable hunger, and a tendency to develop diabetes in adolescence and adulthood when weight was not controlled. Behavioral and psychological problems associated with PWS were not described until the 1980s3. Since these first reports, knowledge on different aspects of the syndrome has vastly increased, although a lot of questions still remained and needed to be further investigated. This chapter describes the genetic basis of PWS, clinical manifestations in different stages of life, the hypothalamus and pituitary, and growth hormone (GH) treatment in children with PWS. It further describes a summary of the results from the Dutch national growth hormone trial for children with Prader-Willi syndrome from 2002 to 2009 and characteristics of PWS within the scope of this thesis. Finally, the objectives of the studies described in the various chapters of this thesis will be presented