Index
Trisomy X (also known as triple X syndrome or 47, XXX) occurs in about 1 in every 1,000 female births.
They are at risk for developmental delays, learning disabilities, and difficulties with psychosocial adjustment, while demonstrating significant individual variability.
Importantly, only a minority of the expected number of women with 47, XXX is ever diagnosed, it is estimated that only 13% of women with trisomy X are diagnosed in their lifetime.
Half of all women diagnosed with 47, XXX are not diagnosed before adulthood.
Causes of XXX syndrome
Triple X syndrome occurs in about 1 in 1,000 girls. On average, five to ten girls with Triple X syndrome are born in the United States each day.
In a study of 50 women with 47, XXX, 90% of the extra X chromosome was obtained maternally.
Molecular studies indicated that 64% of these were the result of meiosis I nondisjunction, 18% were the result of meiosis II nondisjunction, and 16% were the result of postzygotic disjunction or.
In another 31 conceptuses with 47, XXX karyotypes, 93.5% were the result of maternal nondisjunction with increasing maternal age present in meiosis I errors but not in meiosis II errors.
There is no excessive intrauterine mortality after amniocentesis.
Symptoms of XXX syndrome
Characteristic physical findings are minimal; women with X chromosome trisomy cannot be identified by the presence of distinctive physical differences at any age. Average birth weights are somewhat lower than for 46, XX girls.
Many 47, XXX girls will reach the 80th percentile for height during adolescence. The greater height seems to be attributable to the increased growth of the lower segment in relation to the trunk.
The variability is large and height is also influenced by the heights of the parents in the usual multifactorial way. Relative microcephaly is present in a minority, but the mean head circumference is significantly smaller.
Those who have been followed prospectively from birth have a higher incidence of minor abnormalities such as more common features include epicanthic folds , hypertelorism, and clinodactyly.
Rates of renal and genitourinary malformations are increasing and there is an increased risk of premature ovarian failure.
Intelligence, personality and behavior
Neuromotor deficits with a greater tendency to delays in the acquisition of gross motor skills are frequently present and generally mild, but can result in poor coordination and reduced athleticism.
Neurological findings can include hypotonia , developmental delays, intention tremor, and motor skill deficits. Seizure disorders occur in approximately 15% of diagnosed cases.
Developmental delays and cognitive impairments can also be associated with trisomy X, and variability in the presence and severity of problems should be emphasized again.
To a greater extent than other people with sex chromosome abnormalities, women with 47, XXX karyotypes often lag behind in acquiring language and academic skills.
Prospective studies of newborns with trisomy X identified developmental delays of up to 80%, with speech development typically more affected than motor skills.
The IQ is usually 10-15 points lower than that of siblings, but mental retardation (IQ <70) is rare.
Cognitive scores fell into a standard distribution with a full half-scale IQ at 85-90, with general weaknesses in verbal skills, although non-verbal skills were also affected in a percentage of patients.
Psychological features including shyness, attention difficulties, anxiety disorders (including selective mutism), depression , adjustment disorders, and psychotic disorders have also been associated with trisomy X; however, more research is needed on psychiatric disorders.
The increased risk of social and psychological problems should be considered from infancy to adulthood, and the necessary psychological and psychopharmacological interventions should be used.
Gonadal function and fertility
The vast majority of adult women with an extra X chromosome probably go through puberty in the usual way, it is no different with respect to their sexual orientation, and they lead a normal sex life.
Most also have normal reproductive abilities and have children without sex chromosomal aneuploidy. Precocious puberty, early-onset menarche, and primary or secondary amenorrhea, including premature ovarian failure, have also been reported, and premature ovarian failure appears to be more prevalent than in controls.
The incidence of sex chromosomal aneuploidy in daughters of women with 47, XXX does not appear to increase substantially, but has been reported.
Some research indicates that women with triple X may stop producing eggs at a younger age. If that happens, they may go through menopause early and then not be able to get pregnant.
In fact, triple X is often first diagnosed when a woman consults her doctor about fertility problems.
In general, experts note that most women with triple X can become pregnant and deliver healthy babies just like women without triple X.
Diagnosis
The vast majority of women with triple X are never diagnosed, unless they are tested for other medical reasons later in life.
When a girl does not meet developmental milestones, triple X syndrome should be investigated. A team of specialists is better equipped to manage the condition and may include:
- Neurologists.
- Developmental pediatricians.
- Speech therapists and occupational therapists.
- Mental health experts.
XXX syndrome can be diagnosed by a blood test that can look at a person’s chromosomes (karyotype). EEG abnormalities may be present.
Triple X syndrome can be diagnosed prenatally through amniocentesis or chorionic villus sampling.
In Denmark, between 1970 and 1984, 76% of fetuses diagnosed prenatally with triple Xs were aborted. In 1987, this figure was reduced to 56%. With improved information, the number of abortions decreased.
In the Netherlands, between 1991 and 2000, 33% (18/54) of couples who were faced with a prenatal diagnosis of 47, XXX chose to abort.
If balanced information is provided to prospective parents before birth, the incidence of voluntary termination (abortion) is reduced.
Experts agree that girls who receive early intervention can do just as well as girls without the condition.
Those diagnosed with triple X syndrome should also be monitored by their healthcare provider. Some women with this disorder may have heart and kidney problems.
Treatment
The chromosome error that causes Triple X syndrome cannot be repaired, so there is no cure for the syndrome itself.
Treatment recommendations are similar to those for Klinefelter syndrome and XYY syndrome (also called superman syndrome), with an emphasis on interventions for developmental delays and academic problems. A stable home environment can improve some of the symptoms.
Options that may be helpful include:
Regular checkups: Your daughter’s doctor may recommend regular checkups during childhood.
Starting treatments such as speech and physical therapy and counseling early can prevent problems later. Most girls with Triple X can lead normal, healthy lives, especially when they are diagnosed and treated early.
Make sure your daughter has a supportive environment. Both you and your daughter can benefit from these strategies:
Connect with Others : Support groups provide help and support to people with X and Y chromosome disorders and their families. You can also contact associations for X and Y chromosome variations.
Find Disability Support Resources – Facing a learning disability is challenging. An example is the National Center for Learning Disabilities. Ask your daughter’s school or therapist about additional resources.
Find Ways to Relieve Stress – It’s natural to feel overwhelmed at times. Take the time to do something you love to do. Seek the help of outside caregivers who can give you a break from time to time.
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-foot-9-inch (176-cm) tall, 128-pound (58.2-kg) woman who had premature ovarian failure at age 19; her mother was 41 years old and her father was 40 at the time of her conception.
Jacobs, et al . The 47, XXX woman was called a “superwoman,” a term that 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 fly of the Drosophila fruit.
British pathologist and geneticist Bernard Lennox , the chief medical consultant for the Oxford English Dictionary, suggested the term “XXX syndrome.”
