Down’s Syndrome — 2015 Paper I

Approach

• Demand of Question: Explain the chromosomal basis, major phenotypic features and forms of Down syndrome.
• Structuring the Response: Define trisomy 21, explain mechanisms producing it, list characteristic manifestations and mention diagnosis.
• Key Dimensions to Cover: Chromosome 21, nondisjunction, translocation, mosaicism, maternal age, physical features, intellectual disability and prenatal diagnosis.

Model Answer

Introduction: Down syndrome is a chromosomal disorder caused by the presence of additional genetic material from chromosome 21, most commonly resulting in trisomy 21.

The normal chromosome number is:

46 → Down syndrome commonly 47, +21

Major types

1. Free trisomy 21: Usually produced by meiotic nondisjunction; it constitutes the great majority of cases.
2. Translocation Down syndrome: Extra chromosome-21 material becomes attached to another chromosome, often through a Robertsonian translocation.
3. Mosaic Down syndrome: Only some cells possess trisomy 21 because nondisjunction occurs after fertilization.

Characteristic features

Common manifestations include:

• characteristic facial appearance;
• epicanthic folds;
• flat facial profile;
• hypotonia;
• short stature;
• single transverse palmar crease in some individuals;
• varying degrees of intellectual disability.

Congenital heart defects and certain other medical problems occur with increased frequency.

Maternal age

Risk of meiotic nondisjunction increases significantly with advancing maternal age, although Down syndrome can occur at any maternal age.

Diagnosis may involve:

• prenatal screening;
• chorionic villus sampling;
• amniocentesis;
• chromosomal analysis.

Conclusion: Down syndrome is an important example of autosomal numerical chromosomal abnormality, illustrating the relationship between meiotic errors, genotype and human phenotypic development.