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Sex chromosome abnormalities

Carlos A Bacino, MD, FACMG
Section Editor
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Elizabeth TePas, MD, MS


Sex chromosome abnormalities are due to numeric abnormalities (eg, aneuploidies such as monosomy X) or structural defects (eg, isochromosome Xq leading to Turner syndrome) involving the X and Y chromosomes. Congenital sex chromosome abnormalities occur in at least 1 in 448 births [1]. (See "Genetics: Glossary of terms" and "Genomic disorders: An overview".)

Other congenital cytogenetic abnormalities are discussed in detail separately. (See "Congenital cytogenetic abnormalities" and "Microdeletion syndromes (chromosomes 1 to 11)" and "Microdeletion syndromes (chromosomes 12 to 22)" and "Microduplication syndromes".)


The most common sex chromosome aneuploidies are 45,X (Turner syndrome); 47,XXY (Klinefelter syndrome); 47,XYY (XYY syndrome); and 47,XXX, which have birth frequencies of approximately 1 in 2500, 1 in 500 to 1 in 1000, 1 in 850 to 1 in 3000, and 1 in 1000, respectively [2-7]. Sex chromosome mosaicism involving a normal cell line is not unusual. The two most common forms of sex chromosome mosaicism are 45,X/46,XX and 45,X/46,XY [8,9]. The severity of the phenotype in patients with mosaicism is related to the percentage of abnormal cells among critical tissues [10,11].

Monosomy X (45,X or Turner syndrome) — Most patients with Turner syndrome have monosomy for the X chromosome with a 45,X karyotype. Other forms of Turner include mosaicism for X chromosome monosomy (eg, 45,X/46,XX) or 45,X/46,XY mosaic with or without a partial deletion of the Y chromosome. The remaining patients have a structural abnormality of the second X chromosome (eg, an isochromosome of the long arm of X or a deletion involving the short arm of one X). Deletions involving the distal portion of the short arm of the Y chromosome are associated with the Turner phenotype because these individuals are missing the so-called "anti-Turner" genes (SHOX, RPSY4, and ZFY). Deletions of the short arm of the X chromosome are also associated with a Turner phenotype [12]. Most cases represent sporadic events. (See '45,X/46,XX mosaicism' below and '45,X/46,XY mosaicism' below and 'Isochromosome Xq' below and 'Xp22 SHOX deletions' below.)

Turner syndrome is characterized by short stature. Dysmorphic features are common and include low and posteriorly rotated ears, webbing of the neck, shield-like chest (broad chest with wide-spaced nipples), cubitus valgus, short fourth metacarpals, and hypoplastic nails. Other frequent findings include lymphedema, pigmented nevi, and congenital heart defects. Lymphedema in the dorsum of hands and feet may be the only clinical feature seen in newborns. The heart defects typically involve the left outflow tract, and coarctation of the aorta is a common finding. In addition, Turner patients develop streak gonads with ovarian failure and pubertal delay. Renal anomalies can also occur (horseshoe kidneys). Individuals with Turner syndrome that carry Y chromosome material (as is seen in some patients with mosaicism) are at increased risk of developing gonadoblastoma. (See "Clinical manifestations and diagnosis of Turner syndrome" and "Management of Turner syndrome".)

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Literature review current through: Oct 2017. | This topic last updated: Jan 31, 2017.
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