What Is Triple X Syndrome?

Triple X syndrome is characterized by the presence of an extra X chromosome in each cell of a female. The condition is also known as trisomy X and 47 XXX.

Those affected are often taller than average. Usually there is no other physical differences and normal fertility. Occasionally there are learning difficulties, decreased muscle tone, seizures, or kidney problems.

Triple X syndrome occurs in around 1 in 1,000 girls. On average, five to ten girls with triple X syndrome are born in the United States each day.

Triple X is due to a random event. Triple X can result either during the division of the mother’s reproductive cells or during division of cells during early development. It is not typically inherited from one generation to the next. A form where only a percentage of the body cells contain XXX can also occur. Diagnosis is by chromosomal analysis.

Treatment may include speech therapy, physical therapy, and counseling. It is estimated that 90% of those affected are not diagnosed as they either have no or only few symptoms. It was first identified in 1959.

Symptoms Of Triple X Syndrome

Because the vast majority of triple X females are never diagnosed, it may be very difficult to make generalizations about the effects of this syndrome. The samples that were studied were small and may be nonrepresentative. Because of the lyonization, inactivation, and formation of Barr bodies in all female cells, only one X chromosome is active at any time.

Thus, triple X syndrome most often has only mild effects, or has no effects. The symptoms vary from person to person, with some women being more affected than others.

Symptoms may include tall stature, vertical skinfolds that may cover the inner corners of the eyes (epicanthal folds), poor muscle tone, and a curve in the 5th finger towards the 4th. There may also be a small head (microcephaly). There are seldom any observable physical anomalies in triple X females, other than being taller than average.

Poor coordination may be present. Those affected appear to have higher rates of scoliosis.

Females with triple X syndrome often have delayed language development. On average those affected have IQs that are 20 points lower. Poor self-esteem, anxiety, and depression are also common.

Causes

Triple X syndrome is not inherited, but usually occurs as an event during the formation of reproductive cells (ovum and sperm). An error in cell division called nondisjunction can result in reproductive cells with additional chromosomes.

For example, an oocyte or sperm cell may gain an extra copy of the X chromosome as a result of the non-disjunction. If one of these cells contributes to the genetic makeup of a child, the child will have an extra X chromosome in each of her cells. In some cases, trisomy X occurs during cell division in early embryonic development.

Some females with triple X syndrome have an extra X chromosome in only some of their cells. These cases are called 46,XX/47,XXX mosaics.

People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY).

Diagnosis

The vast majority of triple X women are never diagnosed, unless they undergo tests for other medical reasons later in life. Triple X can be diagnosed by a blood test which is able to look at a person’s chromosomes (karyotype). Abnormalities on the electroencephalography may be present.

Triple X syndrome can be diagnosed prenatally through amniocentesis or chorionic villus sampling. In Denmark, between 1970 and 1984, 76% of the prenatally diagnosed fetuses with triple-X were aborted.

Between 1985-1987, this figure dropped to 56%. With improved information, the number of abortions diminished. In the Netherlands, between 1991 and 2000, 33% (18/54) of the couples that were confronted with a prenatal diagnosis of 47,XXX elected to abort. If balanced information is provided to prospective parents, pre-natally, the incidence of voluntary termination (abortion) is reduced.

Image: Epicanthal folds and hypertelorism in 2 year old girl with trisomy X. Credit: Nicole R Tartaglia, Susan Howell, Ashley Sutherland, Rebecca Wilson, and Lennie Wilson CC BY 2.5