A Case of Adult Male Fertility Disorder Caused by Ring Chromosome 4

doi:10.12280/gjszjk.20250348

Abstract

Abstract:

Ring chromosome 4 is a rare chromosomal structural abnormality with significant clinical heterogeneity. We report a case of an adult male patient with multiple malformations including microcephaly, micrognathia, hooked nose, short stature, congenital heart defects, and azoospermia. The patient was scheduled for surgery due to a bladder malignancy, and requested fertility preservation before the operation. However, multiple semen analyses indicated azoospermia, and a percutaneous testicular sperm aspiration showed no sperm in both testes. Pathological examination revealed approximately 40 seminiferous tubules with a small number of spermatocytes and a few sperm, and a Johnsen score of 8. Chromosome karyotype analysis showed mos 46,XY,r(4)(?p16.3?q35) [94]/46,XY[6]. It was suggested that the patient undergo microdissection testicular sperm extraction and sperm cryopreservation during the bladder tumor resection. However, due to malignant tumor and other factors, the patient ultimately decided to forgo fertility preservation and only underwent radical tumor surgery. The patient typically presents with multiple system dysfunctions such as growth retardation and abnormal fertility. It is necessary to complete the chromosomal G-banding karyotype analysis and related molecular-level examinations as soon as possible. After diagnosis, genetic counseling should be actively carried out, and assisted reproductive technology should be utilized in a timely manner to better achieve eugenics and good childbearing.

Key words: Ring chromosomes, Chromosomes, human, pair 4, Azoospermia, Fertility, Case reports

LI Wen-an, FU Sheng-lan, FAN Wen, HOU Zhi-jin, YANG Xiao-ling, MENG Yu-shi. A Case of Adult Male Fertility Disorder Caused by Ring Chromosome 4[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(6): 464-467.

Figures/Tables 2

References 17

[1]	Jacobs PA, Frackiewicz A, Law P, et al. The effect of structural aberrations of the chromosomes on reproductive fitness in man. II. Results[J]. Clin Genet, 1975, 8(3):169-178. doi: 10.1111/j.1399-0004.1975.tb01490.x.
[2]	Carter R, Baker E, Hayman D. Congenital malformations associated with a ring 4 chromosome[J]. J Med Genet, 1969, 6(2):224-227. doi: 10.1136/jmg.6.2.224. pmid: 5801472
[3]	Nishigaki S, Hamazaki T, Saito M, et al. Periventricular heterotopia and white matter abnormalities in a girl with mosaic ring chromosome 6[J]. Mol Cytogenet, 2015,8:54. doi: 10.1186/s13039-015-0162-3.
[4]	Kosztolányi G, Brecevic L, Bajnòczky K, et al. Mosaic supernumerary ring chromosome 1 in a three-generational family: 10-year follow-up report[J]. Eur J Med Genet, 2011, 54(2):152-156.doi: 10.1016/j.ejmg.2010.11.015. pmid: 21145991
[5]	Paz-Y-Miño C, Proaño A, Verdezoto SD, et al. Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review[J]. BMC Med Genomics, 2019, 12(1):167. doi: 10.1186/s12920-019-0614-4. pmid: 32293439
[6]	Strehle EM, Yu L, Rosenfeld JA, et al. Genotype-phenotype analysis of 4q deletion syndrome: proposal of a critical region[J]. Am J Med Genet A, 2012, 158A(9):2139-2151. doi: 10.1002/ajmg.a.35502.
[7]	Paththinige CS, Sirisena ND, Kariyawasam UG, et al. Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature[J]. Case Rep Genet, 2016,2016:4645716. doi: 10.1155/2016/4645716.
[8]	Burgemeister AL, Daumiller E, Dietze-Armana I, et al. Continuing role for classical cytogenetics: Case report of a boy with ring syndrome caused by complete ring chromosome 4 and review of literature[J]. Am J Med Genet A, 2017, 173(3):727-732. doi: 10.1002/ajmg.a.38063. pmid: 28127864
[9]	Blackett PR, Li S, Mulvihill JJ. Ring chromosome 4 in a patient with early onset type 2 diabetes, deafness, and developmental delay[J]. Am J Med Genet A, 2005, 137(2):213-216. doi: 10.1002/ajmg.a.20386.
[10]	Tulloch WS, Newsam JE. Studies on human meiotic chromosomes from testicular tissue[J]. Lancet, 1966, 1(7439):679-682. doi: 10.1016/s0140-6736(66)91627-8. pmid: 4159599
[11]	Yao Q, Wang L, Yao B, et al. Meiotic prophase I defects in an oligospermic man with Wolf-Hirschhorn syndrome with ring chromosome 4[J]. Mol Cytogenet, 2014,7:45. doi: 10.1186/1755-8166-7-45.
[12]	Jung K, Shin KS, Son BR, et al. The Discordance between G-Banding Karyotyping and Microarray in Structural Abnormality[J]. Clin Lab,2023 Dec 1; 69(12). doi: 10.7754/Clin.Lab.2023.230513.
[13]	Chen M, Ke X, Liang H, et al. The phenotype and rhGH treatment response of ring Chromosome 15 Syndrome: Case report and literature review[J]. Mol Genet Genomic Med, 2021, 9(12):e1842. doi: 10.1002/mgg3.1842.
[14]	Nishikawa K, Itoi F, Nagahara M, et al. The normality of sperm in an infertile man with ring chromosome 15: a case report[J]. J Assist Reprod Genet, 2018, 35(2):251-256. doi: 10.1007/s10815-017-1061-9.
[15]	Rajesh H, Freckmann ML, Chapman M. Azoospermia and paternal autosomal ring chromosomes: case report and literature review[J]. Reprod Biomed Online, 2011, 23(4):466-470. doi: 10.1016/j.rbmo.2011.05.013. pmid: 21843971
[16]	Bershteyn M, Hayashi Y, Desachy G, et al. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells[J]. Nature, 2014, 507(7490):99-103. doi: 10.1038/nature12923.
[17]	Li P, Dupont B, Hu Q, et al. The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes[J]. HGG Adv, 2022, 3(4):100139. doi: 10.1016/j.xhgg.2022.100139.