Overview of Triple X syndrome
Triple X syndrome is the most frequent sex chromosome anomaly in females. It is also called Trisomy X or 47, XXX syndrome. Triple X syndrome is a genetic disorder wherein females, who generally have two ‘X’ chromosomes in all cells, have three ‘X’ chromosomes instead.
How common is Triple X syndrome?
Newborn screening studies have revealed that the incidence of Trisomy X is approximately 1 in 1000 female births, of which only around 10% of cases are clinically proven.
How does Triple X syndrome occur?
In typical 46 XX females, only one X chromosome in each cell is genetically active, and the other is inactive. It is theorised that Trisomy X results from over-expression of the genes on the X chromosome that escape X-inactivation.
What are the risk factors for Triple X syndrome?
There is a statistically significant correlation between Trisomy X with advancing maternal age.
What effects does Triple X syndrome have on the body?
There is a wide variation in the manifestation of Triple X syndrome, with some individuals being mildly affected and others having significant physical and psychological features.
The common phenotypical features of Triple X Syndrome include:
- epicanthal folds,
- hypertelorism,
- upslanting palpebral fissures,
- clinodactyly,
- overlapping digits,
- pes planus and
- pectus excavatum.
Pubertal onset and sexual development are usually normal in Triple X Syndrome. However, there are reports of cases with ovarian or uterine dysgenesis.
Premature ovarian failure (POF) is a problem wherein the ovarian functions of hormone production and oocyte (egg) development become impaired before the typical age of menopause.
There have been multiple case reports of women with trisomy X presenting with POF. Precocious puberty has also uncommonly been reported.
Babies with Trisomy X usually have a normal length and weight at birth for gestational age; however, stature typically increases in early childhood.
Some of the other features seen as part of Trisomy X are:
- Tall stature >75th percentile, 80-89%
- Hypotonia in infancy, 55-71%
- Genitourinary malformations, 5-16%
- Seizure disorder, 11-15%
- Intention tremor, 6-20%
- Congenital hip dysplasia, 2-12%
- Constipation/Abdominal pain, 12-45%
- Premature ovarian failure
What other problems can a baby with Triple X syndrome have?
Babies and children with Triple X Syndrome have an increased risk of other medical problems, such as:
- Genitourinary abnormalities, including unilateral kidney and renal dysplasia to ovarian malformations.
- Congenital heart defects have been described, including cases of atrial and ventricular septal defects, pulmonic stenosis and aortic coarctation.
- Seizure disorders and EEG abnormalities in Trisomy X vary between 0 – 65 %.
- Seizure subtypes, including absence, partial, and generalised seizures, with good responses to standard anticonvulsant treatment, have been described.
- Gastrointestinal problems, with many patients commonly presenting with constipation and abdominal pain, are also common concerns.
- Infants and toddlers have been reported to have early developmental delays, especially in motor and speech development.
- Walking may be delayed, with children presenting with gait abnormalities and poor joint stability. Attention deficits and decreased cognitive and adaptive functioning skills may also impact social and educational functioning.
- Mental health problems, including anxiety, depression and adjustment disorders, have also been reported in certain studies.
How is Triple X syndrome diagnosed?
Karyotyping is the most standard test used to diagnose Triple X syndrome. Prenatal testing, including amniocentesis or Chorionic Villus Sampling (CVS), are also used to diagnose Triple X syndrome. However, confirmatory studies are recommended after birth by fluorescence in situ hybridisation (FISH).
Can Triple X syndrome be cured?
Triple X has a variable prognosis, with some individuals having minimal manifestations of the disease and others having significant physical, cognitive and psychological involvement.
Each component of the disease is managed, and symptomatic treatment, including therapy, which improves the quality of life of patients.
Conclusion
Triple X syndrome is a genetic disorder that occurs in girls and women, with a wide range of presentations. It is managed symptomatically with the help of a multidisciplinary team to improve the quality of life of the affected patients.
