X and Y Chromosomal Aneuploidies:

 

Babies with a single fully functioning X chromosome, and either a second X chromosome that is structurally damaged, or completely lacks a second X chromosome or a Y chromosome, have a genotype of X0. These babies are diagnosed with Turner syndrome. Individuals with Turner syndrome may have short stature, fertility problems, swelling of the hands and feet, skeletal abnormalities, and kidney problems, among other symptoms. The phenotype of individuals with Turner syndrome is widely variable between individuals (17). Those with Turner syndrome are AFAB, but do have an increased risk of X-linked recessive disorders due to their single functioning X chromosome. Babies born with more than two X chromosomes may have conditions called Trisomy X (XXX) or Tetrasomy X (XXXX), and are AFAB. Many individuals with these conditions have no symptoms at all or minor symptoms. However, Trisomy X is frequently associated with tall stature, decreased muscle tone, renal and genitourinary abnormalities, an increased risk of learning disabilities, and other symptoms (18). Babies with known genotypes of XXY, may be diagnosed with Klinefelter syndrome, which is typically AMAB, or an intersex condition and their sexual assignment may vary depending on their phenotypic presentation. Klinefelter syndrome frequently goes undiagnosed because of the variability in the phenotype, which can include abnormal gonad function, delayed sexual development, decreased testosterone levels, and infertility (26).

 
 

Assigned Sex At Birth

Genetic testing can identify the differences in an individual’s genes that are a part of their genetic code. This is called an individual’s genotype. Each individual has multiple genotypes because the genotype depends on which genes or chromosomes are being described. Both before and after birth, not all prospective parents choose, or are offered, genetic testing to screen the fetal chromosomes for variants or unexpected results. For babies who have not had any genetic testing, their genotype is unknown, so they are assigned a sex at birth based on the phenotypic, or outwardly visible, appearance of the baby’s sex organs. For babies with known genotypes whose phenotypic appearance of the external sex organs matches what is expected of the genotype are assigned either male or female at birth. Those with one X chromosome and one Y chromosome per cell have a genotype of XY and are Assigned Male at Birth (AMAB). Babies with genotypes of two X chromosomes per cell, XX, with matching external phenotypes are Assigned Female at Birth (AFAB). Assigned Sex at Birth may vary from an individual’s sex later in life when more information is known. Sex and gender are not the same thing and one can have a different gender identity than their assigned sex.

Written by Abigail Sayers; Images by Abigail Sayers unless otherwise noted

Reviewed and Edited by Rachel Baer, MSc, and Andy McCarty, MS, LGC, CGC

Learn More About Genetics:

Citations

  1. Basta M, Pandya AM. Genetics, X-Linked Inheritance. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557383/

  2. Furman B. et al. Sex Chromosome Evolution: So Many Exceptions to the Rules, Genome Biology and Evolution, Volume 12, Issue 6, June 2020, Pages 750–763, https://doi.org/10.1093/gbe/evaa081

  3. Shvetsova E., Sofronova, A., Monajemi, R. et al. Skewed X-inactivation is common in the general female population. Eur J Hum Genet 27, 455–465 (2019). https://doi.org/10.1038/s41431-018-0291-3

  4. Garber K., Visootsak J. & Warren S. Fragile X syndrome. Eur J Hum Genet 16, 666–672 (2008). https://doi.org/10.1038/ejhg.2008.61. 

  5. Barisic N., Claeys K.G., Sirotković-Skerlev, M., Löfgren, A., Nelis, E., De Jonghe, P. and Timmerman, V. (2008), Charcot-Marie-Tooth Disease: A Clinico-genetic Confrontation. Annals of Human Genetics, 72: 416-441. https://doi.org/10.1111/j.1469-1809.2007.00412.x 

  6. Szigeti K., Lupski J. Charcot–Marie–Tooth disease. Eur J Hum Genet 17, 703–710 (2009). https://doi.org/10.1038/ejhg.2009.31

  7. Lim, K. R., Maruyama, R., & Yokota, T. (2017). Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug design, development and therapy, 11, 533–545. https://doi.org/10.2147/DDDT.S97635 

  8. Yue B. (2014). Biology of the extracellular matrix: an overview. Journal of glaucoma, 23(8 Suppl 1), S20–S23. https://doi.org/10.1097/IJG.0000000000000108 

  9. Tantawy AAG. (2010). Molecular genetics of hemophilia A: Clinical perspectives. Egypt J Hum Genet, 11(2), 105-114. https://doi.org/10.1016/j.ejmhg.2010.10.005 

  10. Konkle BA, Nakaya Fletcher S. Hemophilia A. In: GeneReviews®. University of Washington, Seattle, Seattle (WA); 1993. 

  11. Franchini, M., Gandini, G., Di Paolantonio, T. and Mariani, G. (2005), Acquired hemophilia A: A concise review. Am. J. Hematol., 80: 55-63. https://doi.org/10.1002/ajh.20390  

  12. Kashtan C. E. (2021). Alport Syndrome: Achieving Early Diagnosis and Treatment. American journal of kidney diseases : the official journal of the National Kidney Foundation, 77(2), 272–279. https://doi.org/10.1053/j.ajkd.2020.03.026 

  13. Shoulders, M. D., & Raines, R. T. (2009). Collagen structure and stability. Annual review of biochemistry, 78, 929–958. https://doi.org/10.1146/annurev.biochem.77.032207

  14. Savige, J., Colville, D., Rheault, M., Gear, S., Lennon, R., Lagas, S., Finlay, M., & Flinter, F. (2016). Alport Syndrome in Women and Girls. Clinical journal of the American Society of Nephrology : CJASN, 11(9), 1713–1720. https://doi.org/10.2215/CJN.00580116 

  15. Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Lysosomes. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9953/ 

  16. Bernardes, T. P., Foresto, R. D., & Kirsztajn, G. M. (2020). Fabry disease: genetics, pathology, and treatment. Revista da Associacao Medica Brasileira (1992), 66Suppl 1(Suppl 1), s10–s16. https://doi.org/10.1590/1806-9282.66.S1.10  

  17. U.S. Department of Health and Human Services. (n.d.). Turner syndrome - about the disease. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/7831/turner-syndrome   

  18. Tartaglia, N.R., Howell, S., Sutherland, A. et al. A review of trisomy X (47,XXX). Orphanet J Rare Dis 5, 8 (2010). https://doi.org/10.1186/1750-1172-5-8 

  19. Duchenne Muscular Dystrophy (DMD) . Muscular Dystrophy Association. (2021, April 28). https://www.mda.org/disease/duchenne-muscular-dystrophy/causes-inheritance  

  20. The Trustees of the University of Pennsylvania. (n.d.). Carrier Screening. Pennmedicine.org. https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/obstetrics/prenatal-genetic-testing/diagnosis-and-screening-services/carrier-screening 

  21. Gregg, A.R., Aarabi, M., Klugman, S. et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 23, 1793–1806 (2021). https://doi.org/10.1038/s41436-021-01203-z

  22. Romero, S., Rink, B., Biggio, J., & Saller, D. (2017). Committee opinion no. 690: Carrier screening in the age of genomic medicine. Obstetrics & Gynecology, 129(3). https://doi.org/10.1097/aog.0000000000001951  

  23. ACOG Committee on Practice Bulletins (2007). ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstetrics and gynecology, 109(1), 217–227. https://doi.org/10.1097/00006250-200701000-00054 

  24. Minear, M. A., Alessi, S., Allyse, M., Michie, M., & Chandrasekharan, S. (2015). Noninvasive prenatal genetic testing: Current and emerging ethical, legal, and Social Issues. Annual Review of Genomics and Human Genetics, 16(1), 369–398. https://doi.org/10.1146/annurev-genom-090314-050000 

  25. Centers for Disease Control and Prevention. (n.d.). Chorionic villus sampling and amniocentesis: Recommendations for prenatal counseling. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/preview/mmwrhtml/00038393.htm 

  26. Gravholt, C., Chang, S., Wallentin, M., Fedder, J., Moore, P., & Skakkebæk, A. (2018). Klinefelter syndrome: Integrating Genetics, neuropsychology, and endocrinology. Endocrine Reviews, 39(4), 389–423. https://doi.org/10.1210/er.2017-00212