What are the implications if a fetus is confirmed to have Trisomy X (Triple X syndrome) or XXX syndrome?

From the Guidelines

Trisomy X (Triple X syndrome) is generally associated with mild or no significant health implications for the fetus, and most girls with this condition develop normally with no major physical abnormalities. The condition is characterized by an extra X chromosome in females, and its effects can vary widely 1. According to the American College of Medical Genetics and Genomics (ACMG), noninvasive prenatal screening (NIPS) can detect Trisomy X with high accuracy, with a detection rate of 99.6% and specificity of 99.8% 1.

Key Implications of Trisomy X

• Most girls with Trisomy X develop normally and have no major physical abnormalities
• Some individuals may experience mild developmental delays, particularly in speech and language skills, learning disabilities, or slightly lower IQ compared to siblings
• There may be an increased risk of anxiety, depression, or attention difficulties
• Physically, these girls tend to be taller than average, and some may experience early menopause later in life
• No specific medications or treatments are required prenatally or at birth

Recommendations

• Developmental monitoring is recommended after birth, with early intervention services if delays are identified
• Genetic counseling is advisable for the family to understand the condition fully
• It's essential to note that Trisomy X occurs randomly during cell division and is not inherited, with a prevalence of approximately 1 in 1,000 female births 1
• The prognosis is generally good, with most women leading healthy, independent lives with normal fertility

Important Considerations

• Patients receiving confirmatory results should be referred to professionals who can provide an accurate depiction of the phenotype 1
• The potential for neurobehavioral differences related to Trisomy X should be discussed, along with the most recent evidence of medical interventions that may mitigate some of those outcomes 1

From the Research

Implications of Trisomy X (Triple X syndrome) or XXX syndrome

• Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX) 2
• The most common physical features include tall stature, epicanthal folds, hypotonia, and clinodactyly, while seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings 2
• Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years 2
• Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population 2

Prenatal and Postnatal Diagnosis

• Prenatal diagnosis of trisomy X is common, and patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed 2
• Postnatal diagnosis is often indicated by developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF 2
• A study comparing prenatal versus postnatal diagnosis found that prenatally diagnosed females have better neurodevelopmental outcomes, including higher verbal and general ability index scores, and adaptive functioning scores 3

Parental Experience and Genetic Counseling

• Parents of children with prenatally identified trisomy X experience an emotional journey of adapting to the diagnosis, including negative diagnostic experiences, hopeful early childhood, persistent ambiguity, and coping with uncertainty 4
• Genetic counseling should provide expectant parents with current research specific to trisomy X, facilitate connections with other parents of young girls with trisomy X, introduce developmental monitoring approaches, and be prepared to support families with a range of emotional responses to the diagnosis and decisions regarding disclosure 4
• Prenatal diagnosis and prognosis of triple X syndrome should be carefully considered, and expectant parents should be counseled as to the significance of the 47, XXX karyotype and prognostic information must be given 5

Limitations of Diagnostic Techniques

• Chromosomal microarray analysis (CMA) may not detect chromosomal aberrations, such as sex chromosome aneuploidy, in some cases 6
• This limitation should be taken into consideration in similar cases where CMA is used in a clinical setting 6