Psychiatric disorders and behavioral problems in children with Prader-Willi syndrome and the effects of growth hormone treatment

Abstract

This thesis includes studies about developmental, behavioral and psychiatric characteristics in children with Prader-Willi syndrome (PWS). Endocrinologists Prader, Labhart, and Willi were the first describing the combination of neonatal hypotonia, short stature, hypogonadism, hyperphagia and obesity, developmental delay and cognitive impairment in 1956. It was not until the 1980s that behavioral and psychiatric problems in adults with PWS were investigated. However, studies about psychiatric disorders in children are very limited and the few publishes are case reports. This chapter provides an overview of the genetic cause, developmental course, behavioral phenotype, and psychiatric disorders in children with PWS. Subsequently, the objectives of the studies described in the following chapters are presented. Finally, an overview is presented of the Dutch PWS Cohort Study.

__ Prader-Willi syndrome__

PWS is a neurogenetic developmental disorder caused by the absence of expression of genes on the paternally inherited chromosome 15 at the locus q11-q13, due to a paternal deletion (DEL), maternal uniparental disomy (mUPD), imprinting defects or paternal chromosomal translocation. Occurrence is not associated with gender, race or socialeconomic status. The estimated birth incidence is 1:15,000. Main characteristics are hypotonia, hypogonadism, short stature if not treated with growth hormone, obesity, intellectual disability with an IQ between 50-80 and behavioral problems. Characteristic facial features include narrow temporal distance and nasal bridge, almond-shaped eyes, strabismus, a thin-upper lip, and hypopigmentation of hair, eyes, and skin, relative to other family members . Children with PWS have sweet personalities, but the syndrome is also characterized by behavioral problems, social difficulties and psychiatric symptoms . At birth, the infant has typically a low birth weight for gestational age and severe hypotonia causing failure to thrive. During childhood, however, mostly between the age of two and five years, there is a change towards increasing weight and the development of hyperphagia which can lead to excessive eating behavior and severe obesity.