Konstitutionelle Entwicklungsverzögerung und Familiärer und Idiopathischer Kleinwuchs auf dem Prüfstand - Unterscheidbare Klinische Diagnosen oder Existenz eines Kontinuums?

Short stature is a common concern in pediatric practice and stature is known to be highly heritable (heritability approx.80%). Constitutional delay in growth and puberty (CDGP, defined via small stature - less than 3rd age- and sex-specific percentile -, bone age retardation of at least one year and the absence of any other specific underlying disorder), familial short stature (FSS, short stature and lower confidence limit of adult target height as determined from parental heights also below 3rd percentile) and idiopathic short stature (ISS, short stature, no underlying disorder) are considered normal variations in growth and seem to cluster in families. To investigate whether these clinical definitions represent useful entities for molecular genetic studies, we retrospectively collected clinical and anthropometrical data on 156 children and their parents who presented because of short stature at the endocrinological out-patient unit of the University Childrens Hospital Gießen in 2000 - 2002. We find that 24.5% of these children were diagnosed with CDGP, 7.5% with FSS, 29.5% with both and 8.2% with ISS. When comparing the two differentiating features, bone age retardation (CDGP vs. FSS and ISS) and target height (FSS vs. CDGP and ISS), we do not find bimodal distributions which would be expected if the conditions are clearly distinct. In the CDGP and ISS groups, parental heights are mostly just above the threshold for FSS and in the FSS and ISS groups many children also have delayed bone age, but less than one year. Growth and pubertal development of parents were not different in the groups. The large overlap of 29.5% with CDGP and FSS also underlines the close relationship between these conditions. We conclude that the clinical differentiation as based on the thresholds for target height and bone age retardation does not reflect a truly different underlying etiology.