Growth retardation in turner syndrome: Aneuploidy, rather than specific gene loss, may explain growth failure

The etiology of short stature (SST) in Turner syndrome (TS) is still a subj ect of speculation. A variety of hypotheses have been put forward, from SST as a result of increased intrauterine tissue pressure after fetal lymphede ma to haploinsufficiency of a specific growth gene(s). These hypotheses hav e various statistical-auxological implications on the growth distribution i n TS. Empirical research has provided no clear evidence for any of these th eories, but the well known correlation between patients' and midparental he ight (MPH) could be established. The influence of undetected mosaic status has often been cited as a major problem in the investigation of growth in T S. However, an assessment of mosaic status (simultaneous analysis of karyot ype and phenotype) and its effect on growth with inclusion of MPH has been not yet carried out for a large sample. The aim of this study was to evalua te growth and its complex relationship to mosaic status and MPH in TS. In a mixed cross-sectional and longitudinal study we retrospective analyzed the auxological and clinical data of 447 patients with a pure loss of X-ch romosomal material (n = 381 with 45,X0; n = 66 mosaics). The 447 patients w ere selected from a series of 609 consecutive patients with TS. To assess t he effect of mosaic status on growth, we computed a bifactorial analysis of variance (phenotype, karyotype), including MPH as a covariate. In line with the mosaic hypothesis, we found a correlation between individu al loss of X-chromosomal material and phenotypical expressivity. In contras t, no correlation was found with respect to growth. With respect to MPH, we found growth retardation (GR) even in those patients with "normal" height above the third percentile (-2 or more so score). The interindividual variance of GR in TS (comparable to growth variance in the normal population) seems to be unrelated to other TS-specific factors ( e.g. mosaic status or single gene loss). Instead, both interindividual vari ance and the global growth shift distribution are best explained by the pre sence of an unspecific aneuploidic effect. Furthermore, consideration of pa tient height in relation to MPH should lead to a better understanding of th e nature of GR in TS than the commonly used, strictly qualitative definitio n of SST.