Tall stature, insulin resistance, and disturbed behavior in a girl with the triple X syndrome harboring three SHOX genes: offspring of a father with mosaic Klinefelter syndrome but with two maternal X chromosomes

Abstract

Aims: To describe the tall stature and its possible underlying mechanism in a Caucasian girl (age 12 years and 10 months) with 46,XX (28%)/47,XXX (72%) mosaicism and to identify the parental origin of her extra X chromosome.

Methods: The fasting glucose-to-insulin ratio was studied. The karyotypes of the girl and her parents as well as the presence of SHOX copies and the parental origin of her extra X chromosome were assessed.

Results: Clinical examination revealed a tall stature and severe acne, and endocrinological/metabolic assessment revealed insulin resistance. Fluorescence in situ hybridization cytogenetic analysis depicted the presence of three SHOX genes in the 47,XXX cell line of the patient. Karyotyping of her parents showed a normal 46,XX karyotype in the mother and 46,XY(93%)/47,XXY(7%) Klinefelter mosaicism in the father. However, DNA analysis unequivocally showed maternal origin of the extra X chromosome of the patient.

Conclusions: This report suggests that SHOX gene triplication may produce a tall stature, even in the presence of preserved ovarian function. X triplication might predispose to insulin resistance and behavioral disorders.