
Trisomy X

Trisomy X, also known as triple X syndrome and 47,XXX, is a genetic condition in which a female has an extra X chromosome. Those affected are often taller than average. Usually there are no other physical differences and normal fertility. Occasionally there are learning difficulties, decreased muscle tone, seizures, or kidney problems.
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 occurs in about one in every 1,000 female births. 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.
Signs and symptoms.
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. A person with triple X syndrome will have two Barr bodies in each cell, leading to most persons having only mild effects or no effects. The symptoms vary from person to person, with some people being more affected than others.
Physical.
Symptoms may include tall stature, vertical skin folds that may cover the inner corners of the eyes (epicanthal folds), poor muscle tone, and a curve in the 5th finger towards the 4th (clinodactyly). 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.
Psychological.
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, as are autistic features.
Cause.
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.
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. By 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, prenatally, the incidence of voluntary termination (abortion) is reduced.
Treatment.
A stable home environment can improve some of the symptoms.
Epidemiology.
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.
History.
The first published report of a woman with a 47,XXX karyotype was by Patricia A. Jacobs, et al. at Western General Hospital in Edinburgh, Scotland, in 1959. It was found in a 35‑year-old, 5 ft. 9 in. (176 cm) tall, 128 lb. (58.2 kg) woman who had premature ovarian failure at age 19; her mother was age 41 and her father was 40 at the time of her conception. Jacobs, et al. called the 47,XXX woman a "superfemale", a term which was immediately criticized, did not gain acceptance, and was based on the incorrect assumption that the sex-determination system in mammals was the same as in the fruit fly "Drosophila". British pathologist and geneticist Bernard Lennox, the principal consultant on medical terms for the "Oxford English Dictionary", suggested the term "XXX syndrome".
Growth and development.
The table below describes development in triple X syndrome in relation to age. In each postnatal age group, you can see the psychological and behavioural development.