Sex chromosome abnormalities are due to numeric abnormalities (eg, aneuploidies such as monosomy X) or structural defects (eg, genomic disorders such as MECP2 duplication syndrome). Congenital chromosomal abnormalities occur in at least 1 in 400 births . (See "Glossary of genetic 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".)
NUMERIC ABNORMALITIES (ANEUPLOIDIES)
The most common sex chromosome aneuploidies are 45,X (Turner syndrome); 47,XXY (Klinefelter syndrome); 47,XYY; and 47,XXX, which have birth frequencies of approximately 1/2500, 1/500 to 1/1000, 1/900 to 1500, and 1/1000, respectively [2-7]. Sex chromosome mosaicism involving a normal cell line is not unusual. The two most common sex chromosome mosaicisms 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 [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 the X-chromosome (eg, 45,X/46,XX) or are a 45,X/46,XY mosaic with 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 . 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 together with some of the following features: dysmorphic features including low and posteriorly rotated ears, webbing of the neck, shield like chest (broad with wide-spaced nipples), lymphedema, cubitus valgus, short fourth metacarpal, hypoplastic nails, pigmented nevi, and congenital heart defects. 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). Lymphedema in the dorsum of hands and feet may be the only clinical features seen in newborns. Individuals with Turner syndrome that carry Y chromosome material (some mosaic Turner) are at increased risk of developing gonadoblastoma. Turner syndrome is discussed in detail separately. (See "Clinical manifestations and diagnosis of Turner syndrome (gonadal dysgenesis)" and "Management of Turner syndrome (gonadal dysgenesis)".)