What is triple x?

History and Symptoms

In 1914, Calvin Blackman Bridges discovered nondisjunction of sex chromosomes in the fruit fly, Drosophila melanogaster. In 1925, he proposed the genic or sex balance theory, which defined the relationship between sex chromosomes and autosomes (A) for sex determination. According to this theory, the following ratios of sex chromosomes and numbers of sets of autosomes determine what sex phenotype will emerge in humans. For example, XX + 2 sets of autosomes (2X:2A, ratio = 1.0) = normal female; XY + 2 sets of autosomes (1X:2A, ratio = 0.5) = normal male; and XXX + 2 sets of autosomes (3X:2A, ratio = 1.5) = metafemale, or superfemale.

The term “metafemale” was first applied to the XXX (triple X) condition by Curt Stern around 1959. The US National Library of Medicine stated in 2014 that the frequency of the triple X phenotype in the general human population was approximately one in one thousand newborn girls. The XXX females are characterized by the presence of two Barr bodies in their cells. They have a total of 47 chromosomes instead of the normal complement of 46.

Affected individuals have variable fertility, ranging from normal to sterile. They may be phenotypically normal but are often slightly taller than average, with longer legs. These individuals may have widely spaced nipples and a webbed neck. Studies have shown that most affected individuals lead a normal sexual life and have normal children. In some cases, menstruation may begin at an older age, menstrual cycles may be irregular or temporarily interrupted, and menopause may begin earlier compared to normal XX women. Abnormal kidney development and seizures may occur in as many as 10 percent of those with triple X syndrome, as reported by the US National Library of Medicine.

Genetic Cause

The basic causes of XXX females are best explained through meiosis, the cell division that halves the number of chromosomes in gametes, and nondisjunction. From a single human cell (46 chromosomes) designated for sexual reproduction, meiosis produces four cells, each with 23 chromosomes. Thus, normal human eggs carry one-half (22A + 1X = 23) of the total number of chromosomes (44A + 2X = 46). Occasionally, a mistake occurs during meiosis, called nondisjunction. Nondisjunction during meiosis I or meiosis II can produce eggs with 2X chromosomes (22A + 2X = 24). Usually the nondisjunction that gives rise to XXX females occurs in the female parent during meiosis I.

Fertilization of an egg carrying two X chromosomes by an X-bearing (22A + 1X = 23) sperm results in an individual with 44A + 3X = 47 chromosomes, or triple X. The extra X chromosome is not usually transmitted to the children. Thus, affected individuals can have normal children. Triplo-X, trisomy X, and 47 XXX are also the names given to the triple X phenotype. This genetic condition has also been referred to as extra X aneuploidy, multiple X syndrome, or metafemale.

Social Issues

The intelligence quotient (IQ) of affected individuals is usually low normal to normal. In some studies, IQ was found to be lower by 30 points than that of their normal siblings; only a few had an IQ lower than 70. Language learning in XXX children is usually delayed. Emotional maturation may also be delayed. These delays in development are preventable by providing increased psychological, social, and motor stimulation both at home and at school. Tutoring is often needed at some time during development.

The 47 XXX condition can put some affected individuals at risk for speech disorders, learning disabilities, and neuromotor deficits, which ultimately could lead to decreased psychosocial adaptation, especially during adolescence. One study found young females with 47 XXX to be less well adapted in both their teen and adult years; they described their lives as more stressful. On average, they experienced more work, social, and relationship problems than their siblings. Affected individuals may encounter behavioral problems, including mild depression, conduct disorder, immature behavior, and socializing problems. Good parenting and a supportive home may assure a better social and behavioral development.

Key Terms



autosomes

:

all chromosomes other than sex chromosomes in a cell nucleus




Barr body

:

named after its discoverer, Murray L. Barr, a dark-stained sex chromatin body in nuclei of females, which represents the inactivated X chromosome; the number of Barr bodies in any cell is generally one less than the number of X chromosomes




Lyon hypothesis

:

proposed by Mary Lyon in 1962, a hypothesis that during development one of the two X chromosomes in normal mammalian females is inactivated at random; the inactivated X chromosome is a Barr body





meiosis


:

the process by which gametes (sperm and eggs) are produced in sexually reproducing organisms





nondisjunction


:

the failure of homologous chromosomes to disjoin during meiosis I, or the failure of sister chromatids to separate and migrate to opposite poles during meiosis II





sex chromosomes


:

the homologous pair of chromosomes that determines the sex of an individual; in humans, XX is female and XY is male; XX females produce one kind of gamete, X (homogametic sex), and XY males produce two kinds of gametes, X and Y (heterogametic sex)





Bibliography

Bender, B., et al. “Psychological Competence of Unselected Young Adults with Sex Chromosome Abnormalities.” American Journal of Medical Genetics 88.2 (1999): 200–206. Print.

Jones, Kenneth Lyons, Marilyn Crandall Jones, and Miguel del Campo Casanelles. “XXX and XXXX Syndromes.” Smith’s Recognizable Patterns of Human Malformation. 7th ed. Philadelphia: Elsevier Saunders, 2013. Print.

Migeon, Barbara R. Females Are Mosaics: X Inactivation and Sex Differences in Disease. 2nd ed. New York: Oxford UP, 2014. Print.

Redei, G. P. Genetics Manual. River Edge: World Scientific, 1998. Print.

Rovet, J., et al. “Intelligence and Achievement in Children with Extra X Aneuploidy.” American Journal of Medical Genetics 60.5 (1995): 356–63. Print.

"Triple X Syndome." Genetics Home Reference. US National Library of Medicine, June 2014. Web. 1 Aug. 2014.

Walsh, Beth. "Chromosomal Abnormalities." Health Library. EBSCO, May 2014. Web. 1 Aug. 2014.