what causes down syndrome in fetus

Trisomy 21: Genetic Etiology and Developmental Implications

Genetic Basis of the Condition

This condition typically arises from the presence of an extra (third) copy of chromosome 21. This is referred to as trisomy 21. It can manifest in several forms:

  • Non-disjunction: The most common type, occurring when chromosome 21 fails to separate properly during meiosis in either the egg or sperm. This results in a gamete with an extra copy of the chromosome.
  • Translocation: In a small percentage of cases, part or all of chromosome 21 becomes attached to another chromosome (usually chromosome 14). While the individual may have the usual two copies of chromosome 21 material, the attached segment leads to the characteristics associated with the syndrome.
  • Mosaicism: A less frequent occurrence where some cells have the typical chromosome count, while others have trisomy 21. The proportion of cells with trisomy 21 can vary, potentially affecting the severity of characteristics.

Parental Origin and Recurrence Risk

In cases involving non-disjunction, the extra chromosome 21 originates more frequently from the maternal side. The recurrence risk varies depending on the specific type of genetic event:

  • For non-disjunction, the recurrence risk is generally low, but slightly elevated compared to the general population, and is age-dependent for the mother.
  • For translocation, the recurrence risk is significantly higher, particularly if one of the parents is a balanced translocation carrier. Genetic counseling is essential to determine the specific risk.
  • Mosaicism in a parent could also potentially lead to elevated risk.

Prenatal Screening and Diagnostic Testing

Screening Tests

Non-invasive prenatal screening (NIPS) using cell-free DNA from the maternal blood sample can assess the probability of this chromosomal variation. Other screening tests include the combined first trimester screen (nuchal translucency ultrasound and blood tests) and the quad screen (blood tests).

Diagnostic Tests

Chorionic villus sampling (CVS) and amniocentesis are invasive diagnostic procedures that can definitively confirm the presence of trisomy 21 by analyzing fetal chromosomes. These tests carry a small risk of miscarriage.

Associated Developmental Characteristics

The presence of an extra copy of chromosome 21 affects multiple organ systems and developmental pathways. This can lead to a range of characteristic physical features and developmental differences. The severity and specific presentation vary widely among individuals.