E-Poster Presentation ESA-SRB-ANZBMS 2021

Y am I Male (#431)

Sneha Vidyasagar 1 , Durgesh Gowda 1 , Amy Hsieh 1
  1. Endocrinology, Toowoomba Hospital, Toowoomba, QLD, Australia

Introduction: 

Isodicentric Y Chromosome (IDYC) is the most common chromosomal structural anomaly and may not be diagnosed until adulthood. IDYC presents with complications that need monitoring and management by endocrinologists.

Case: 

A 28-year-old male was referred for low libido on a background of Hashimoto’s thyroiditis. Examination revealed short stature (150cm), Tanner stage 5 secondary sexual characteristics, a right testis measuring 18ml with an absent left testis and hypospadias. Sex Hormone profile was consistent with primary hypogonadism. Semen Analysis revealed azoospermia. Peripheral Karyotyping showed mosaicism with (90%)45,XO and (10%)46,X,isodicentric Y.  FISH study located a breakpoint and fusion at 11.2222 on the Y chromosome. Computed Tomography revealed a left intra-abdominal gonad, which was removed. On Histology, the presumed undescended testis was a Mullerian structure consisting of a fallopian tube and rudimentary uterus. Karyotyping of this showed mosaic IDYC anomalies.

Discussion: 

Male sex differentiation is determined by the SRY gene and hormones including AMH and Testosterone1. Disruption of this leads to disorders of sex development.

Breakage and deletion along the Y chromosome and fusion of sister chromatids, leads to the formation of IDYC2. Phenotypic manifestations are determined by mosaicism and what genetically important components of the Y chromosome are deleted 3.  Common phenotypes include Turner syndrome, infertility, gonadal dysgenesis and short stature.

IDYC accounts for 10-15% of male infertility4. If oligospermia is present, testicular sperm extraction can be performed. For those not wanting fertility, testosterone replacement improves outcomes5. The risk of testicular cancer in dysgenetic gonads is increased and requires annual ultrasonography surveillance6.70% have a short stature due to the deletion of the SHOX gene4. The benefit of Growth Hormone replacement for this cohort is conflicted. 

Conclusion:

Management of IDYC must be individualised given the heterogeneous phenotypes. This includes assessing gonadal malignancy risk, hormonal replacement and assisted reproductive techniques.

  1. Rey R, Josso N, Racine C .(2020). Sexual Differentiation. Endotext [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279001/
  2. Beaulieu Bergeron, M., Brochu, P., Lemyre, E., & Lemieux, N. (2011). Correlation of intercentromeric distance, mosaicism, and sexual phenotype: molecular localization of breakpoints in isodicentric Y chromosomes. American journal of medical genetics. Part A, 155A(11), 2705–2712. https://doi.org/10.1002/ajmg.a.34260
  3. Yang, Y., & Hao, W. (2019). Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes. Molecular cytogenetics, 12, 55. https://doi.org/10.1186/s13039-019-0465-x
  4. Dumeige, L., Chatelais, L., Bouvattier, C., De Kerdanet, M., Hyon, C., Esteva, B., Samara-Boustani, D., Zenaty, D., Nicolino, M., Baron, S., Metz-Blond, C., Naud-Saudreau, C., Dupuis, C., Léger, J., Siffroi, J. P., Donadille, B., Christin-Maitre, S., Carel, J. C., Coutant, R., & Martinerie, L. (2018). Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?. European journal of endocrinology, 179(3), 181–190. https://doi.org/10.1530/EJE-18-0309
  5. Bassil, N., Alkaade, S., & Morley, J. E. (2009). The benefits and risks of testosterone replacement therapy: a review. Therapeutics and clinical risk management, 5(3), 427–448. https://doi.org/10.2147/tcrm.s3025
  6. 6. Carlotto, J. R., Colleoni-Neto, R., Shigueoka, D. C., Artigiani-Neto, R., & Lopes-Filho, G. (2015). INTRA-ABDOMINAL SEMINOMA TESTIS IN ADULT: CASE REPORT. Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery, 28(4), 296–297. https://doi.org/10.1590/S0102-6720201500030021