Background: The phenotypic manifestations in the 45,X/46,XY karyotype is diverse and there are challenges in management due to this diversity.
Objective and hypotheses: The aim of this study was to describe the clinical spectrum of 45,X/46,XY mosaicism and variants diagnosed in childhood.
Method: A retrospective review of 20 patients with 45,X/46,XY (n=7) and its variants ((45,X/46,X,der(Y) (n=12)) and 46,X,der(X),t(X;Y) (n=1)) followed at a tertiary center between January 1997 and July 2014 was performed.
Results: The mean age at diagnosis was 5.0 years (range 0.115.1) presenting with genital ambiguity, short stature and delayed puberty. Genital ambiguity was present in 86% of 45,X/46,XY patients and 33% of 45,X/46,X,der(Y) patients (P=0.09). All patients with 45,X/46,XY karyotype (n=7) and 75% of 45,X/46,X,der(Y) karyotype showing ambiguous genitalia (n=4) or signs of virilization (n=1) underwent gonadectomy. Gonadoblastoma was detected in intraabdominal gonads of three phenotypically female patients, of which two were diagnosed at later ages of 9.5 and 13.7 years respectively. Thirteen patients were reared as females while seven were reared as males. External masculinization scores were evaluated (males 9.2 vs females 1.2, P<0.001). Turner characteristics (n=16, 80%), cardiac anomalies (n=3, 20%) and kidney anomalies (n=4, 31%) were present. The percentage of patients with height z-scores less than the third percentile increased from 42% at diagnosis to 68% at growth hormone (GH) treatment initiation (P=0.005). Sixteen patients received GH and showed significant increases in height z-scores (P<0.001). Ten patients achieved final adult height with a median height z-score of −1.07±0.89.
Conclusion: The clinical spectrum of the 45,X/46,XY karyotype is diverse and patients require individualized care. There is a risk for gonadoblastoma even with the 45,X/46,X,der(Y) karyotype showing virilization. Although height progressively decreases from diagnosis, GH has a positive effect on growth and FAH.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology