Down Syndrome, HLA-B27–Associated Diseases and Extractable Nuclear Antigen Test
DNB Orthopaedics • October 2024 • Paper I • 10 Marks
Introduction
Down syndrome is the most common viable chromosomal aneuploidy and is caused by the presence of additional genetic material from chromosome 21. Orthopaedic manifestations are important because affected individuals have characteristic ligamentous laxity, altered skeletal development and joint instability, particularly involving the cervical spine, hip, knee and foot.
HLA-B27 is strongly associated with the group of seronegative spondyloarthropathies. Extractable nuclear antigen testing, in contrast, is primarily used in the evaluation of systemic autoimmune connective-tissue diseases.
I. Down Syndrome
Down syndrome is a chromosomal disorder resulting from the presence of an additional copy, complete or partial, of chromosome 21.
Etiopathogenesis of Down Syndrome
The clinical phenotype results from increased dosage and expression of genes located on chromosome 21, producing abnormalities in growth, neurodevelopment, connective tissue and multiple organ systems.
Cytogenetic Types
| Type | Mechanism | Approximate Frequency |
|---|---|---|
| Free trisomy 21 | Meiotic nondisjunction causing three separate chromosome 21 copies | About 95% |
| Robertsonian translocation | Additional chromosome 21 material attached to another acrocentric chromosome, commonly chromosome 14 or 21 | About 3–4% |
| Mosaicism | Post-zygotic mitotic nondisjunction produces both normal and trisomy-21 cell lines |