(CSEMP057) MONITORING FOR GONADAL CELL TUMOR RISK IN A MALE PATIENT WITH MIXED GONADAL DYSGENESIS WITH A RING Y CHROMOSOME

Abstract:

Background: Mixed gonadal dysgenesis can present with abnormalities in the Y chromosome such as a ring Y chromosome. These children can present with ambiguous genitalia or appear phenotypically male or female. They are at an increased risk of developing gonadal germ cell tumors (GGCTs) that arise from persistent, immature stem cells. The presence of the gonadoblastoma locus (GBY) on the Y chromosome increases this risk, as genes in this locus are involved in cell proliferation. 45X/46XY phenotypic males can present with short stature, cardiorenal malformations and infertility.

Case: A 12-year-old boy was referred for assessment of short stature. He had an antenatal diagnosis of IUGR and linear growth was along the 10thpercentile until age 1, after which he has been tracking less than the 1st percentile. On examination, he was non-dysmorphic and proportionate with a height of 132.5 cm (-3.6 SD) and weight of 31.3 kg (-2.11 SD). His mid-parental height was 170.6cm (-0.81 SD) and a bone age scan obtained was within 1SD. He was phenotypically male with a stretched penile length of 5 cm and bilateral descended testes with testicular volume of 5cc. Chromosomal microarray revealed a ring Y chromosome with SHOX haploinsufficiency and deletion in the AZF region, which is involved in spermatogenesis. A karyotype revealed 45X/46X(r)Y. The ring Y chromosome includes most of the short arm along with the SRY gene, but there is a loss of the terminal end of the short arm containing the SHOX gene and deletion of the entire long arm. Due to the risk of GGCT associated with mixed gonadal dysgenesis, a baseline testicular ultrasound is being obtained prior to discussing the use of growth hormone therapy for SHOX deficiency.

Discussion: The risk of GGCT is lower in phenotypic males with mixed gonadal dysgenesis compared to those with ambiguous genitalia. However, there is an increased risk of GGCT with growth hormone therapy. Whether we use growth hormone therapy or not, this patient will be monitored periodically with physical exams, gonadotropins, serum testosterone, testicular ultrasounds and serum tumor markers. This case highlights the importance of genetic testing for short stature and monitoring closely for tumor risk in male patients with mixed gonadal dysgenesis.