Genetics
Down Syndrome
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Get access- 1:800 live births
- Chromosome 21 is the shortest chromosome and is acrocentric
- Mostly due to chromosomal nondisjunction during meiosis
- >80% during meiosis I
- >95% derived from maternal meiosis
5% have a translocation with another acrocentric chromosome (Note: translocation errors are not related to maternal age
- 2% are mosaics due to non-disjunction during mitosis
- Triple test: can diagnose 65-70%
- Alpha-feto protein (decreased)
- Oestriol (decreased)
- hCG (increased)
- Nuchal scan with bHCG and pregnancy associated protein (PAP): identifies 80%
- Amniocentesis is more sensitive
Hot Topic
Ocular findings in Down syndrome
- Almond palpebral fissure
- Upslanting palpebral fissure
- Prominent epicanthic folds
- Blepharitis and cicatricial ectropion
- Strabismus: esotropic
- Nystagmus: horizontal
- Aberrant retinal vessels at the disc
- Iris stromal hypoplasia and Brushfield spots
- Keratoconus
- Cataract
- Myopia
- Optic atrophy
Summary Table: Genotypes and disease associations
| Disease associations | |
| HLA-B7 and DR2 | Presumed ocular histoplasmosis syndrome (POHS) and multiple sclerosis |
| HLA-DR3 | Thyroid eye disease (also HLA-B8 and genes for CTLA-4)Thygeson’s superficial punctate keratopathy |
| HLA-B8 | Sjogren’s syndrome |
| Myasthenia gravis | |
| Type 1 diabetes | |
| Grave’s disease | |
| Sarcoidosis | |
| Intermediate uveitis | |
| HLA-B27 | Ankylosing spondylitis |
| Psoriatic arthritis | |
| Reiter syndrome | |
| Idiopathic, non-granulomatous iritis | |
| IBD | |
| HLA-B25 | Acute anterior uveitis |
| HLA-B44 | Retinal vasculitis |
| HLA-B51 | Behcet syndrome |
| HLA-B54 | Posner-Schlossman |
| HLA-DR4 | Sympathetic ophthalmia |
Vogt-Koyanagi-Harada syndrome (and HLA-DR1) | |
| Juvenile rheumatoid arthritis | |
| HLA-A29 | Birdshot chorioretinopathy (most consistent association of any disorder) |
| HLA-DR15 | Intermediate uveitis |
| Multiple sclerosis | |
NB: HLAs A, B and C are type 1 MHC molecules (meaning present on all cells except erythrocytes). HLA-D is the type 2 MHC which is present on APCs mainly |