Anatomical characteristics caused by extra sex chromosomes

Sex polysomies are the presence of more than two sex chromosomes in an individual’s genome. The normal genotypes are 46XX, female and 46XY, male. The number refers to the number of chromosomes in the genome, with X and Y as the sex chromosomes (Y is the traditional male sex chromosome). Individuals with polysomy can have genotypes of 47XXY, 47XXX, 47XYY, or even 48XXXY, 48XYYY or 49XXXXY. Just like with other chromosomes, the presence of extra sex chromosomes results in anatomical abnormalities.

Genitalia and secondary sex characteristics

As expected, altered sex chromosome numbers alter the physical manifestation of gender, particularly due to imbalances in hormone levels such as testosterone, estrogen and gonadotropin. X polysomy in males, called Klinefelter syndrome, is considered an endocrine abnormality and leads to hypogonadism (inability to produce sperm and small testes). The 47XXY genotype is the most common cause of hypogonadism in males. Males with Klinefelter’s syndrome also have enlarged breasts, infertility and sparse body hair. In contrast, women with 47XXX (lack of a Y chromosome leads to the female phenotype) often have no discerning anatomical changes. However, approximately half of 48XXXX women have abnormal menstruation, though infertility is not a certainty based on the Tetrasomy and Pentasomy X Support Group.

Y polysomy also has effects on male fertility. 47XYY males have been found to have low sperm counts, but are not necessarily infertile. However, some 47XYY males exhibit female phenotypes due to mosaicism in which some cells are 45X and others are 47XYY (instead of all being 46XY).

Mental and cognitive disorders

Individuals with Klinefelter’s syndrome tend to have psychosocial issues. Clinical descriptions have reported that as the number of X chromosomes increases, so does the extent of mental involvement in the disorder, with mental retardation and low IQ being characteristic of 48XXXX and 48XXXY. Cognitive and emotional issues also appear to accompany Y polysomy, with criminality being studied for decades in 47XYY males. However, with more certainty, 47XYY syndrome has been associated with delayed development of motor skills. 48XYYY has been rarely reported, but is also accompanied by a low IQ.

Skeletal, cardiac and other abnormalities

X polysomy in both males and females tends to be associated with taller stature, especially as the number of chromosomes increases. In addition to tall stature, 48XXXX is also associated with abnormal curvature of the pinkie finger (clinodactyly) and radioulnar synostosis (fusion of the bones in the forearm). It also causes facial abnormalities, including epicanthic folds (extra eyelid skin as seen in Down’s syndrome, a condition caused by trisomy 21), increased space between the eyes (hypertelorism) and uncontrollable eye movements (nystagmus). Y polysomy, particularly 47XYY, has been characterized by congenital hip dislocation at birth, but also tends to cause a taller stature.

Klinefelter’s syndrome has also been associated with cardiac abnormalities and increased risk of autoimmune disorders, such as diabetes, and altered adipose tissue distribution.

Sex polysomies

The manifestation of sex polysomies varies from individual to individual and is based on which sex chromosome is duplicated – and how many times. Because the conditions are rare, clinicians have few cases to compare for each genotype, making it very difficult to tell families of those with the disorders what to expect.