Auxological tools for following growth in extreme short stature and for evaluating growth promoting interventions

Sammanfattning: Growth charts are inevitable tools for following children in clinical practice and also when evaluating growth promoting therapy. Growth is a concern especially for families to children of extreme short stature such as in skeletal dysplasias but evaluations of growth pattern with changes in height position is complicated when height develops far below normal population range. Height gain from growth hormone therapy is variable for short stature conditions without aberrant growth hormone secretion such as in Turner syndrome. This makes it difficult to communicate realistic adult height estimates to concerned families. The first part of this PhD project used semi-longitudinal data from 4,375 measuring occasions to construct growth and body proportion references for achondroplasia and to describe these in relation to normal population references. Typical for achondroplasia, tempo in head size was increased attaining final size earlier than normal. Height was at the same time compromised with major loss in height position during the first years of life, due to limited growth capacity of the legs. At adult ages, leg length was half of that in normal population and arm span almost 35 percent lower than normal contributing to severely reduced area of personal access. Pronounced body disproportions distort the BMI-value in achondroplasia, which is why specific BMI charts were constructed. Clinical achondroplasia charts were developed to support surveillance of these children and, as short stature matrix, possibly also for other children with severe short stature for which syndrome-specific charts are missing. The usability of these achondroplasia charts were tested by illustrating growth pattern of selected skeletal dysplasias. Obtained achondroplasia references for height, sitting height, leg length and arm span might contribute to a better understanding of the effect of FGFR3 signalling on growth and will also be inevitable tools for evaluation of novel treatments. In the second part, variability in response to growth hormone therapy was studied by dividing a sample of 455 girls with Turner syndrome, reported in the Swedish National Register for growth hormone treatment of children and adolescents, into good and poor response based on the distribution of total height gain from treatment. As age at treatment initiation was distributed over almost entire growth period, the sample was further grouped into those with treatment start during normally prepubertal and pubertal ages. Differences of clinical relevance were higher mid-parental height, higher GH dose at 12 months of treatment and improved body proportions in the younger good response group; and younger age and shorter height position at treatment initiation and higher GH dose in the older good response group. These findings could possibly be influenced by subgroups identified in graphic presentations. Initial height gain from treatment did not necessarily translate into better total height gain neither in younger or older poor groups. In contrast to previous claims, early initiation of growth hormone treatment per se did often not result in better total height gain.