Growth in humans, primarily longitudinal growth, is a complex process which starts at conception and proceeds through various developmental stages, mainly controlled by genetic factors and to a... Show moreGrowth in humans, primarily longitudinal growth, is a complex process which starts at conception and proceeds through various developmental stages, mainly controlled by genetic factors and to a lesser degree by environmental, psychosocial and nutritional factors. The GH-IGF-I axis is an important regulator of longitudinal growth, what is evident from the observation that genetic defects in this axis have been shown to be responsible for abnormal growth. These mutations, however, are rare and do not explain the __normal__ variation in height among people. This thesis focuses on the detection of genetic defects in the GH-IGF-I axis that may explain growth disorders. Initially the so-called __candidate gene approach__ was used, examining various genes in the GH-IGF-I axis. After that, a whole genome approach was used to identify novel genes involved in aberrant growth using whole genome microarray studies (SNP-ar rays) and next-generation sequencing. Also, for some genes genotype-phenotype correlations were established. With this we have tried to acquire more insight in the regulation of longitudinal growth Show less
In this thesis, four studies on children and adolescents with Down syndrome are described. The first study showed that the number of live births of children with Down syndrome in the Netherlands... Show moreIn this thesis, four studies on children and adolescents with Down syndrome are described. The first study showed that the number of live births of children with Down syndrome in the Netherlands remained stable over the period 1997-2007 on 14.6 per 10,000 births. Of these, 85% were live born. In the second study is observed that growth retardation in children with Down syndrome meanly occurs in three critical periods of growth, resulting in shorter final stature and smaller head circumference than the general Dutch population shows. Furthermore, Dutch children with Down syndrome have alarmingly high prevalence rates of overweight and obesity during childhood and adolescence. The third study showed that eight-year-old children with Down syndrome have an average developmental delay of four years, more often have emotional and behavioral problems, and have a less favorable health-related quality of life (HRQoL) compared with children from the general population. Children with Down syndrome and recurrent respiratory tract infections showed relatively more delayed development. In the fourth study, results showed that adolescents with Down syndrome remain dependent to a large degree and have serious difficulties in functioning socially. Additionally, results showed that serious problem behavior is highly prevalent in adolescents with Down syndrome. Show less
