Chromosomal diseases caused by numerical autosomal aberrations: trisomy 21, trisomy 13, trisomy 18.
Numerical autosomal aberrations are chromosomal disorders caused by the presence of an extra autosome (trisomy). They usually arise from meiotic nondisjunction, leading to an abnormal chromosome number (aneuploidy).
Autosomal trisomies have more severe clinical consequences than sex chromosome aneuploidies because autosomes contain a large number of essential genes.
The three most important autosomal trisomies compatible with live birth are:
- Trisomy 21 (Down syndrome)
- Trisomy 18 (Edwards syndrome)
- Trisomy 13 (Patau syndrome)
General Mechanisms of Autosomal Trisomy
1. Meiotic Nondisjunction
- Failure of homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to separate.
- Results in gametes with n + 1 chromosomes.
- Strong association with advanced maternal age.
2. Mosaicism
- Postzygotic mitotic nondisjunction.
- Produces two cell lines (e.g., 46/47).
- Leads to milder phenotype.
3. Robertsonian Translocation
- Fusion of long arms of acrocentric chromosomes.
- Important especially in Down syndrome.
- Can be inherited from a balanced carrier parent.
General Pathophysiology
- 1. Presence of an extra autosome → gene dosage imbalance.
- 2. Overexpression of multiple genes disrupts embryonic development.
- 3. Abnormal organogenesis affects brain, heart, face, and internal organs.
- 4. Severity depends on:
- chromosome involved,
- degree of mosaicism,
- mechanism of trisomy.