We hypothesized that because 45,X/46,XY (X/XY) children share a cell line with Turner syndrome (TS), they also share co-morbidities described in TS. In addition, the presence of the Y chromosome in brain and in other body tissues would influence their function. On the basis of our findings, we aimed to establish optimal procedures for clinical evaluation, management, and follow-up of these children. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. In January of 2005, we started retrospective record review of all X/XY children in combination with cohort follow-up (of those who had not reached adult height) until August of 2009. The study included review of clinical presentation, clinical characteristics, diagnostic measures, radiologic studies, karyotype studies, psycho-endocrinology evaluation, and growth-promoting treatments. There was no specific intervention. Phenotype reflected cell line distribution. The presence of 45,X cell line explains how X/XY children have abnormalities similar to girls with TS, while presence of Y chromosome explains why they have tomboyish behavior. In conclusion, these children require clinical evaluation similar to that performed in female children with TS, including cardiovascular, renal, endocrine, growth and development, autoimmune, psychological, and educational evaluation. Specific management needs to be tailored to the presence of Y chromosomal material.

Background: Growth pattern of children with 45,X/46,XY karyotype (X/XY children) has not been characterized. Objective: Our objective is to describe growth pattern and long-term outcome of X/XY children and to develop guidelines for management of their short stature. Our hypothesis was that abnormal karyotype and deficiency of gonadal function might play a role in growth deceleration in X/XY children. Methods: Retrospective record review and cohort follow-up of X/XY children were conducted between January 2005 and August of 2009. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. The main outcome measures were clinical presentation, clinical characteristics, growth pattern, radiologic studies, pathological studies, and endocrine function of X/XY children. Results: Only X/XY female children underwent bilateral gonadectomy. As a group, X/XY female children were shorter at all age groups and at adult height relative to X/XY male children. Both groups manifested growth deceleration rather than growth spurt at the time of puberty. In both groups, adult height was compromised relative to mid-parental height. Conclusions: X/XY children, similar to girls with Turner syndrome, benefit from growth hormone treatment. Deficiencies of both hypothalamic gonadal axis and primary gonadal function appear to play a role in their growth deceleration. Sex steroid replacement at the time of puberty has an important role in management.

Duplication of the DAX1 gene on the X chromosome with normal sex determining region of Y (SRY) results in 46 XY sex reversal. This was inherited from the mother who had normal ovarian function. Additional problems include growth failure, mental retardation and multiple congenital anomalies. The baby did not have a mutation or deletion of DAX1, which would have caused adrenal insufficiency and hypogonadism.