Sex Chromosome Abnormalities

Abstract

In human subjects, the sex chromosomes are the X and the Y chromosomes. Normally, a complement of two X chromosomes (46,XX) is seen in females and one X and one Y (46,XY) in males. The X‐chromosome includes about 1500 genes, only a few of which are involved in sex development. The Y‐chromosome contains very few genes, but one gene, SRY, is the most important gene in male sex development. Multiple autosomal genes are also involved in sex development. Abnormalities of sex chromosomes can involve errors in the number of sex chromosomes, such as 45,X0 (Turner syndrome), 47,XXX, 47,XXY (Klinefelter syndrome), 47,XYY or mosaicism. Sex chromosome abnormalities also include aberrations of a single gene of the sex chromosome, leading to a disorder of sex development (DSD). This can result in 46,XX DSD and 46,XY DSD.

Key Concepts

  • Turner syndrome occurs when females have a missing sex chromosome (45,X0) or have a mosaic complement of cells with one or more lines missing a sex chromosome.
  • Girls with Turner syndrome have a variety of congenital anomalies, the most striking being short stature and premature ovarian failure.
  • Klinefelter syndrome boys (47,XXY) have tall stature, marfinoid habitus, and may have difficulty with language development and verbal IQ (intelligent quotient).
  • 46,XY complete gonadal dysgenesis, or Swyer syndrome, describes patients who have both external and internal female organs with a 46,XY chromosome complement.
  • 46,XY disorders of sex development encompass a wide range of disorders including androgen insensitivity, partial gonadal dysgenesis and many more.
  • 46,XX disorders of sex development can result from a multitude of virilising disorders or the presence of Y‐chromosome material.
  • Patients with disorders of sex development and intra‐abdominal gonads may be at risk for gonadoblastoma, depending on their underlying disorder.
  • Assignment of sex, timing of surgery and medical management of patients with disorders of sex development is controversial.

Keywords: Turner syndrome; Klinefelter syndrome; triple X syndrome; the 47,XYY syndrome; 46,XX DSD; 46,XY DSD; gonadal dysgenesis; androgen insensitivity; Swyer syndrome

Figure 1. Sex differentiation pathway.
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References

Bardsley MZ, Kowal K, Levy C, et al. (2013) 47,XYY syndrome: clinical phenotype and timing of ascertainment. Journal of Pediatrics 163 (4): 1085–1094.

Berkovitz GD, Fechner PY, Zacur HW, et al. (1991) Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation. Medicine 70 (6): 375–383.

Bird RJ and Hurren BJ (2016) Anatomical and clinical aspects of Klinefelter syndrome. Clinical Anatomy 29: 606–619.

Colindres JV, Axelrad M, McCullough L, et al. (2016) Evidence‐based management of patients with 45,X/46,XY gonadal dysgenesis and male sex assignment from infancy to adulthood. Pediatric Endocrinology Reviews 13 (3): 585–601.

Ford CE, Jone KW, Polani PE, De Almedia JC and Briggs JH (1959) A sex‐chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet 273 (7075): 711–713.

Granger A, Zurada A, Zurada‐Zielinksa A, Gielecki J and Louikas M (2016) Anatomy of turner syndrome. Clinical Anatomy 29: 638–642.

Groth KA, Skakkebaek A, Host C, Gravhold H and Bojesen A (2013) Klinefelter syndrome: a clinical update. Journal of Clinical Endocrinology and Metabolism 98 (1): 20–30.

Huang H, Wang C and Tian Q (2016) Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis. Gynecological Endocrinology 32 (12): 995–998.

Hughes IA, Houk C, Ahmed SF, Lee PA and LWPES/ESPE Consensus Group (2006) Consensus statement on management of intersex disorders. Archives of Disease in Childhood 91: 554–563.

Kim IW, Khadilikar AC, Ko EY and Sabanegh ES (2013) 47,XYY syndrome and male infertility. Reviews in Urology 15 (4): 188–196.

Jorgensen A, Johansen ML, Juul A, et al. (2015) Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development. Seminars in Cell & Developmental Biology 45: 124–137.

Linden MJ, Bender BG, Harmon RJ, Mrazek DA and Robinson AR (1988) 47,XXX: what is the prognosis? Pediatrics 82: 619–630.

Maier EM, Leitner C, Lohrs U and Kuhnle U (2003) True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene. Journal of Pediatric Endocrinology and Metabolism 16: 575–580.

Délot EC and Vilain EJ (2003) Nonsyndromic 46,XX Testicular Disorders of Sex Development. 2003 Oct 30 [Updated 2015 May 7]. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1416/.

Mohnach L, Fechner PY and Keegan CE (2016) Nonsyndromic Disorders of Testicular Development. 2008 May 21 [Updated 2016 Jun 2]. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1547/.

Mongan NP, Tadokoro‐Cuccaro R, Bunch T and Hughes IA (2015) Androgen insensitivity syndrome. Best Practice & Research Clinical Endocrinology & Metabolism 29: 569–580.

Migeon CJ, Berkovitz GD and Brown TR (1994) Sexual differentiation and ambiguity. In: Blizzard R, Kappy M and Migeon C (eds) Wilkins: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence, 4th edn, pp. 573–715. Springfield, IL: Thomas Books.

McInnes R, Thompson M and Willard H (1991) The sex chromosomes and their abnormalities. In: Thompson and Thompson Genetics in Medicine, 6th edn, pp. 231–246. Philadelphia, PA: W.B. Saunders Company.

van Niekerk WA and Retief AE (1981) The gonads of human true hermaphrodites. Human Genetics 58: 117–122.

Otter M, Schrander‐Stumpel C and Curfs L (2010) Triple X syndrome: a review of the literature. European Journal of Human Genetics 18 (3): 265–271.

Sorenson K (1992) Physical and mental development of adolescent males with Klinefelter syndrome. Hormone Research 37 (suppl. 3): 55–61.

Tartaglia NR, Howell S, Sutherland A, Wilson R and Wilson L (2010) A review of Trisomy X (47,XXX). Orphanet Journal of Rare Diseases 5: –8.

Vasundhera C, Jyotsna VP, Kandasamy D and Gupta N (2016) Clinical, hormonal, and radiological profile of 46,XY disorders of sexual development. Indian Journal of Endocrinology and Metabolism 20 (3): 300–307.

Further Reading

Aittomäk K (1994) The genetics of XX gonadal dysgenesis. American Journal of Human Genetics 54: 844–851.

Brenner S and Miller JH (2002) Encyclopedia of Genetics. San Diego, CA: Academic Press.

Carpenter SEK and Rock J (2000) Pediatric and Adolescent Gynecology, 2nd edn. Philadelphia, PA: Lippincott Williams and Wilkins.

Fechner PY, Marcantonio SM, Ogata T, et al. (1993) Report of a kindred with X‐linked 46,XY partial gonadal dysgenesis. Journal of Clinical Endocrinology and Metabolism 76: 1248–1253.

Jones KL (1997) Smith's Recognizable Patterns of Human Malformations, 6th edn. Philadelphia, PA: Elsevier Saunders.

Lifshitz F (2003) Pediatric Endocrinology, 4th edn. New York, NY: Marcel Dekker, Inc.

Linden MG, Bender BG and Robinson MD (1990) Clinical manifestations of sex chromosome anomalies. Comprehensive Therapy 16 (5): 3–10.

Scriver CR, Beaudet AL, Sly WS and Valle D (2001) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York, NY: McGraw‐Hill.

Tijo JH and Levan A (1956) The chromosomal number of man. Hereditas 42: 1.

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Pappas, Kara B, and Migeon, Claude J(Jan 2017) Sex Chromosome Abnormalities. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005943.pub2]