1. Numerical Abnormalities (Aneuploidy)

Occur when there is an extra or missing chromosome due to errors in meiosis (nondisjunction).

Common Examples:

• Down Syndrome (Trisomy 21)
  • Extra copy of chromosome 21.
  • Features: Intellectual disability, characteristic facial features (flat face, upward-slanting eyes), heart defects, increased risk of leukemia.
• Edwards Syndrome (Trisomy 18)
  • Extra copy of chromosome 18.
  • Features: Severe intellectual disability, clenched fists, rocker-bottom feet, heart defects; most infants do not survive past one year.
• Patau Syndrome (Trisomy 13)
  • Extra copy of chromosome 13.
  • Features: Cleft lip/palate, polydactyly, severe brain defects; high mortality in infancy.
• Turner Syndrome (Monosomy X, 45,X)
  • Missing one X chromosome in females.
  • Features: Short stature, webbed neck, infertility, heart defects, learning difficulties.
• Klinefelter Syndrome (47,XXY)
  • Extra X chromosome in males.
  • Features: Tall stature, infertility, gynecomastia, learning/behavioral challenges.
• Triple X Syndrome (47,XXX)
  • Extra X chromosome in females.
  • Features: Tall stature, mild learning disabilities; many cases go undiagnosed.
• XYY Syndrome (47,XYY)
  • Extra Y chromosome in males.
  • Features: Tall stature, possible learning/behavioral issues; often undiagnosed.

---

2. Structural Abnormalities

Occur when parts of chromosomes are missing, duplicated, or rearranged.

Common Types:

• Deletions (Loss of a chromosome segment)
  • Cri-du-chat Syndrome (5p-)
    • Deletion on chromosome 5.
    • Features: High-pitched cry (like a cat), intellectual disability, microcephaly.
  • Williams Syndrome (7q11.23 deletion)
    • Features: Elfin-like facial features, cardiovascular disease, hyper-social personality.
• Duplications (Extra copies of a segment)
  • Charcot-Marie-Tooth Disease (CMT1A, dup 17p12)
    • Features: Peripheral neuropathy, muscle weakness.
• Translocations (Exchange of segments between chromosomes)
  • Balanced Translocation (No genetic material lost; carrier may be healthy but at risk for unbalanced offspring).
  • Unbalanced Translocation (Extra or missing genetic material → developmental issues).
  • Philadelphia Chromosome (t(9;22)) → Seen in chronic myeloid leukemia (CML).
• Inversions (Segment flipped in reverse order)
  • Usually harmless unless it disrupts a critical gene.
• Ring Chromosomes
  • Ends of a chromosome fuse into a ring.
  • Can cause growth delays and malformations.
• Isochromosomes
  • One arm is duplicated, and the other is lost.
  • Example: Isochromosome Xq in some Turner syndrome cases.

---

Causes of Chromosomal Abnormalities

• Nondisjunction (Failure of chromosomes to separate during meiosis → aneuploidy).
• Advanced maternal age (Higher risk for trisomies like Down syndrome).
• Radiation/chemical exposure (Can cause breaks in chromosomes).
• Inherited structural rearrangements (e.g., balanced translocation in a parent).

---

Diagnosis & Management

Prenatal Testing:

• Non-invasive prenatal testing (NIPT) – Detects fetal DNA in maternal blood for trisomies.
• Chorionic villus sampling (CVS) & Amniocentesis – Direct chromosomal analysis (karyotype).
• Ultrasound – Detects physical abnormalities (e.g., nuchal translucency in Down syndrome).

Postnatal Testing:

• Karyotyping (Standard chromosome analysis).
• FISH (Fluorescence In Situ Hybridization) – Detects specific deletions/duplications.
• Microarray (aCGH) – Detects small deletions/duplications.

Management:

• No cure for most chromosomal disorders, but supportive care includes:
  • Surgery (e.g., for heart defects in Down syndrome).
  • Hormone therapy (e.g., growth hormone for Turner syndrome).
  • Early intervention programs (Speech, physical, occupational therapy).