Triple X
Triple X syndrome, also known as multiple X syndrome or metafemale, is a genetic condition occurring in females characterized by the presence of an extra X chromosome, leading to a total of 47 chromosomes instead of the typical 46. This condition is estimated to affect about one in every one thousand female births. While many individuals with Triple X syndrome may appear normal and can lead typical sexual and reproductive lives, there can be variations in fertility, with some experiencing challenges in this area.
Common physical traits associated with Triple X include slightly taller stature, longer legs, and in some cases, features such as widely spaced nipples and a webbed neck. Cognitive and developmental aspects may include lower average IQ, language delays, and emotional maturation challenges; however, with appropriate support and education, many individuals thrive. It is also not uncommon for individuals with this extra chromosome to experience behavioral issues, including mild depression and learning disabilities, especially during adolescence. Understanding and supporting those affected by Triple X syndrome can significantly improve their quality of life and social integration.
Triple X
ALSO KNOWN AS: Multiple X syndrome; metafemale
SIGNIFICANCE: Genetic defects are quite common in humans. The frequency of females born with XXX chromosomes, called triple X or multiple X syndrome, generally occurs in about one in one thousand but may be less in some populations. Although most such females have normal appearance and sexual reproduction, this abnormality needs to be better understood so that the affected individuals’ lives can be improved medically and socially.
History and Symptoms
In 1914, Calvin Blackman Bridges discovered 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 (A) for sex determination. According to this theory, the following ratios of sex chromosomes and numbers of sets of autosomes determine what sex 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 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. Many individuals exhibit clinodactyly of the fifth finger. 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 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, X, and 47 XXX are other 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. Attention deficit hyperactivity disorder is seen in some individuals as well. Good parenting and a supportive home may assure a better social and behavioral development.
Key Terms
- autosomesall chromosomes other than sex chromosomes in a cell nucleus
- Barr bodynamed 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 hypothesisproposed 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
- meiosisthe process by which gametes (sperm and eggs) are produced in sexually reproducing organisms
- nondisjunctionthe 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 chromosomesthe 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)
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