Sex Chromosome Aneuploidy

Topic Name Introduction Turner Syndrome Klinefelter Syndrome Triple X Syndrome 47,XYY Syndrome Diagnosis and Management

Introduction to Sex Chromosome Aneuploidy

Sex chromosome aneuploidy refers to numerical abnormalities of the X and Y chromosomes. These conditions are relatively common, occurring in approximately 1 in 400 live births. They result from nondisjunction during meiosis or mitosis and can affect physical, cognitive, and behavioral development to varying degrees.

Key features of sex chromosome aneuploidies include:

• Variable phenotypic expression
• Effects on growth and development
• Impact on fertility
• Potential cognitive and behavioral challenges
• Increased risk of certain medical conditions

Turner Syndrome (45,X)

Turner syndrome is characterized by the presence of only one X chromosome in females.

Genetics:

• Karyotype: 45,X (complete monosomy X)
• Mosaic forms: 45,X/46,XX or 45,X/46,XY
• Structural abnormalities of the X chromosome

Clinical Features:

• Short stature
• Ovarian dysgenesis and infertility
• Characteristic physical features (webbed neck, low hairline, broad chest)
• Cardiovascular abnormalities (coarctation of the aorta, bicuspid aortic valve)
• Renal anomalies
• Hypothyroidism
• Hearing loss
• Normal intelligence with possible specific learning difficulties

Klinefelter Syndrome (47,XXY)

Klinefelter syndrome is the most common sex chromosome disorder in males, characterized by the presence of an extra X chromosome.

Genetics:

• Karyotype: 47,XXY (most common)
• Mosaic forms: 47,XXY/46,XY
• Higher-grade aneuploidies: 48,XXXY; 49,XXXXY (rare)

Clinical Features:

• Tall stature
• Small testes and infertility
• Gynecomastia
• Decreased facial and body hair
• Cognitive and language delays
• Behavioral and social difficulties
• Increased risk of breast cancer and osteoporosis
• Metabolic syndrome and type 2 diabetes

Triple X Syndrome (47,XXX)

Triple X syndrome is characterized by the presence of an extra X chromosome in females.

Genetics:

• Karyotype: 47,XXX (most common)
• Mosaic forms: 47,XXX/46,XX
• Higher-grade aneuploidies: 48,XXXX; 49,XXXXX (rare)

Clinical Features:

• Often mild and nonspecific
• Tall stature
• Mild developmental delays
• Speech and language difficulties
• Learning disabilities
• Behavioral and emotional challenges
• Usually normal fertility
• Increased risk of premature ovarian failure

47,XYY Syndrome

47,XYY syndrome is characterized by the presence of an extra Y chromosome in males.

Genetics:

• Karyotype: 47,XYY
• Mosaic forms: 47,XYY/46,XY (rare)

Clinical Features:

• Often subtle physical features
• Tall stature
• Macrocephaly
• Mild developmental delays
• Speech and language difficulties
• Learning disabilities
• Behavioral issues (impulsivity, ADHD)
• Usually normal fertility
• Increased risk of asthma and seizures

Diagnosis and Management

Diagnosis:

• Prenatal screening: Non-invasive prenatal testing (NIPT)
• Prenatal diagnosis: Chorionic villus sampling (CVS) or amniocentesis
• Postnatal diagnosis: Karyotype analysis
• Clinical suspicion based on physical features and developmental concerns

Management:

• Multidisciplinary approach
• Regular monitoring of growth and development
• Hormone replacement therapy (e.g., estrogen in Turner syndrome, testosterone in Klinefelter syndrome)
• Management of associated medical conditions
• Educational support and interventions
• Speech and language therapy
• Psychosocial support
• Genetic counseling for family planning

Long-term Follow-up:

• Cardiovascular monitoring (especially in Turner syndrome)
• Bone density screening
• Fertility preservation options (when applicable)
• Psychological support throughout life stages
• Vocational guidance and support

Sex Chromosome Aneuploidy

1. What is sex chromosome aneuploidy?
   A condition where an individual has an abnormal number of sex chromosomes
2. What is the most common sex chromosome aneuploidy in females?
   Turner syndrome (45,X)
3. What is the most common sex chromosome aneuploidy in males?
   Klinefelter syndrome (47,XXY)
4. What is the karyotype of Triple X syndrome?
   47,XXX
5. What is the approximate incidence of Klinefelter syndrome?
   1 in 500-1,000 male births
6. Which sex chromosome aneuploidy is also known as Jacob's syndrome?
   47,XYY syndrome
7. What is the primary cause of sex chromosome aneuploidy?
   Nondisjunction during meiosis
8. Which diagnostic test can definitively diagnose sex chromosome aneuploidy?
   Karyotype analysis
9. What is the typical stature of individuals with Turner syndrome?
   Short stature
10. Which hormone is typically deficient in Klinefelter syndrome?
    Testosterone
11. What is a common physical feature in Turner syndrome?
    Webbed neck
12. Which sex chromosome aneuploidy is associated with tall stature?
    47,XYY syndrome
13. What is the fertility status of most males with Klinefelter syndrome?
    Infertile due to azoospermia
14. Which cardiac defect is commonly associated with Turner syndrome?
    Coarctation of the aorta
15. What is the typical cognitive profile in Triple X syndrome?
    Mild learning disabilities and delayed language development
16. Which endocrine disorder is commonly associated with Turner syndrome?
    Primary ovarian insufficiency
17. What is the risk of breast cancer in Klinefelter syndrome compared to typical males?
    Increased risk (about 20 times higher)
18. Which sex chromosome aneuploidy is associated with an increased risk of behavioral problems?
    47,XYY syndrome
19. What is gonadal dysgenesis?
    Incomplete or defective formation of the gonads, often seen in Turner syndrome
20. Which hormone replacement therapy is typically given to girls with Turner syndrome?
    Estrogen replacement therapy
21. What is the approximate incidence of Turner syndrome?
    1 in 2,000-2,500 female births
22. Which sex chromosome aneuploidy is associated with an increased risk of deep vein thrombosis?
    Klinefelter syndrome
23. What is the typical onset of puberty in boys with Klinefelter syndrome?
    Delayed or incomplete puberty
24. Which autoimmune disorder is more common in individuals with Turner syndrome?
    Hashimoto's thyroiditis
25. What is the typical cognitive profile in Klinefelter syndrome?
    Verbal cognitive deficits and learning difficulties
26. Which sex chromosome aneuploidy is associated with macrocephaly?
    47,XYY syndrome
27. What is the role of growth hormone therapy in Turner syndrome?
    To improve final adult height
28. Which psychiatric disorder is more common in individuals with 47,XXY and 47,XXX?
    Anxiety and depression
29. What is the typical appearance of the ovaries in Turner syndrome?
    Streak gonads (undeveloped ovaries)
30. Which non-invasive prenatal test can screen for sex chromosome aneuploidies?
    Cell-free fetal DNA testing

Further Reading

• GeneReviews: Turner Syndrome
• GeneReviews: Klinefelter Syndrome and 47,XXY
• GeneReviews: 47,XXX (Triple X Syndrome) and 47,XYY
• Clinical practice guidelines for the care of girls and women with Turner syndrome
• International clinical practice guidelines for the diagnosis and management of Klinefelter syndrome
• Nature Reviews Endocrinology: Sex chromosome aneuploidies