Origin of the X-chromosome influences the development and treatment outcomes of Turner syndrome

Abstract

Turner syndrome (TS) affects 1/2,500 live-born female infants. In the present study, we attempted to clarify the relationship between genetic factors (especially the X-chromosome origin), clinical features, body/sexual development, and treatment outcomes. We enrolled 39 female infants aged between 3 and 14 years. General demographic and clinical features were documented, and laboratory analysis of blood samples was performed. Subject karyotype was determined by G-banding of 50 peripheral white blood cells, and the parenteral origin of the retained X-chromosome was determined. Next, growth hormone (GH) treatment was prescribed for 12 months, with follow-ups performed as determined. For patient groups separated according to X-chromosome origin, the basal height, bone age, insulin-like growth factor (IGF)-1, and insulin-like growth factor binding protein-3 (IGFBP-3) levels were comparable; however, after the 12-month treatment, significant differences in the height increase and IGF-1 levels were observed. If the X-chromosome (or chromosomes) originated from both parents, the increase in height was less substantial, with lower serum IGF-1 levels. The uterine size, prolactin level, increased weight after treatment, and bone age difference after treatment negatively correlated with the mother’s age at the time of birth. The mother’s height at the time of birth demonstrated a negative correlation with the basal bone age difference and a positive correlation with the IGF-1 level. In summary, the retained X-chromosome derived from both parents is associated with poorer response to GH therapy. The mother’s age and height at the time of birth can strongly impact the patient’s body/sexual development and the response to GH treatment. Thus, the mother’s age and height at the time of birth and the parental origin of the X-chromosome should be carefully considered before developing a treatment plan for TS.