Triple X syndrome (47,XXX)
Epidemiology - Occurs in approximately 1 in 1,000 live female births.
Cause - Meiotic nondisjunction, most commonly during maternal meiosis.
Pathophysiology
• One X chromosome remains active.
• The additional X chromosome undergoes X-inactivation (Barr body formation), but genes that escape X-inactivation are overexpressed.
• Overexpression of these genes accounts for the clinical features.
Clinical Features
Growth
• Tall stature, Long legs, Increased growth velocity during childhood
Neurodevelopment
• Mild developmental delay, Delayed speech and language, Mild motor delay, Hypotonia
• Learning disabilities, Lower average IQ (typically 15–20 points below)
Behavioral/Psychiatric
• ADHD, Anxiety, Social difficulties, Emotional immaturity
• Autism spectrum disorder in a minority
• Depression may occur during adolescence or adulthood
Physical Features
• Epicanthal folds, Hypertelorism, Clinodactyly
• Flat feet, Joint hypermobility
• Mild scoliosis, Dental anomalies
Neurological
• Hypotonia, Coordination difficulties
Renal abnormalities Uncommon
• Renal agenesis, Duplex collecting system, Vesicoureteral reflux
Cardiac defects Uncommon
• Atrial septal defect, Ventricular septal defect, Patent ductus arteriosus
Endocrine/Reproductive
• Normal puberty, Normal secondary sexual characteristics, Normal fertility
Intelligence
• IQ ranges widely.
• Most have mild learning difficulties rather than intellectual disability.
• Verbal skills are often more affected than nonverbal abilities.
