Endocrine Abstracts

Introduction: Patients presenting with isodicentric chromosome Y (idicY) formation in a mosaic karyotype can present with phenotypic features ranging from mixed gonadal dysgenesis, to females with stigmata of Turner’s syndrome. The presence of the SRY gene increases the risk of germ-cell tumours.

Case report: A 12-year-old prepubertal girl was referred for evaluation of extreme short stature (height 122 cm; −4.58 SDS; weight 26.7 kg; and −3.3 SDS). No significant past medical history of note. General examination was normal. Investigations revealed elevated gonadotropins (FSH 81.3 IU/l and LH 15.5 IU/l) indicating ovarian failure and a low IGF1 (86 ng/ml). Her blood karyotype was 45,F(26)/46,X,i(Y)(p11.3)(3).ish i(Y)(p11.3)(SHOX+, SRY+) confirming a female karyotype with two cell lines, the majority cell line showing monosomy X and an idicY with the breakpoint at p11.3. Ultrasound couldn’t identify gonadal tissue on the right and 0.19 ml gonadal tissue on the left. The presence of isochromosome Y (SRY+) raised the possibility of mixed gonadal dysgenesis with an associated risk of germ-cell tumour which led to bilateral gonadectomy. Biopsy revealed ovarian stroma and absence of oocytes, bilateral focal areas of Wolffian structures and minute foci of gonadoblastoma confirming mixed gonadal dysgenesis. She had shown a brilliant response (height velocity 8.43 cm/year; 6.53 SDS) to GH treatment (1.4 mg/m² per day for 1.25 years) and will soon be commenced on estrogen therapy for pubertal induction.

Discussion: IdicY is normally unstable during cell division; most patients reported are chromosomal mosaics, generally including a 45,X cell line. As in our case, patients reported with a high proportion of 45,X cells and idic(Y)p breakpoints at Yp11.2 or 11.3 resulting in a deletion of the distal Yq are usually phenotypically female. The presence of SRY in idicY mosaicism can result in the early presentation of gonadoblastoma requiring early gonadectomy.