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Down’s syndrome
Down’s syndrome

Down’s syndrome

Down’s syndrome (trisomy 21) is a trisomy disorder (extra chromosome) on the 21st chromosome. It affects 1.5 in 1000 births. It is the most common genetic cause of intellectual disability.

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Pathophysiology

We typically have 23 pairs of chromosomes, 46 in total. The first 22 are autosomes while the 23rd one is the sex chromosome.

There are 3 ways of inheriting Down’s syndrome:

  1. Standard trisomy 21/non-disjunction - this means that during meiosis, there was a failure of the chromosome pairs to separate and hence we are left with an extra chromosome.
  2. Robertsonian translocation - 4% of DS cases have 46 chromosomes, of which one is a a Robertsonian translocation between 21q and chromosome 14/21. if there is a 21q21q translocation, 100% of the offspring will have DS with a 21q21q translocation.
  3. Mosaic - 1% of cases have mosaic DS. Some cells will have 2 21st chromosomes, while others will have 3 copies. It is milder than standard trisomy 21 but is variable in its presentation.

😷 Presentation

⭐️ There are characteristic dysmorphic features that are present in almost all DS patients:

  • Short neck
  • Short stature
  • Flattened nose and face
  • Brachycephaly - small head and flat back.
  • Prominent epicanthic folds and upward sloping palpebral fissures.
  • Single palmar crease
  • Brushfield spots on iris
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🚨 Complications

  • Learning disability
  • Recurrent otitis media infections
  • Deafness due to Eustachian tube deformities → glue ear (otitis media with effusion) → conductive hearing loss.
  • Visual problems such as myopia (nearsightedness), strabismus (eyes pointing in different directions) and cataracts.
  • Hypothyroidism
  • Cardiac defects (present in 40-50%)
    • ASD
    • VSD
    • Patent ductus arteriosus
    • Tetralogy of Fallot
  • Dementia
  • Leukaemia (acute lymphoblastic leukaemia)- more common in children with DS.
  • Infertility (males) and sub-fertility (females)
  • Intestinal obstruction

🧰 Management

🥇 Assessment and noting any medical conditions associated with DS such as congenital heart disease. Special consults for medical conditions are required depending on what is present, such as paediatric cardiologist.

🥇 Genetic counselling for the parents is needed once DS is diagnosed.

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MDT:

Supportive care from the MDT allows DS patients to meet their needs. This includes:

  • Occupational therapy
  • Speech therapy
  • Physiotherapy
  • Dietician
  • Paediatrician
  • GP
  • Cardiologist
  • ENT and audiologist
  • Optician
  • Educational services
  • Down’s Syndrome Association and other charities

🔍 Investigations

We will discuss antenatal screening and testing separately:

  • Thyroid checks (every 2 years)
  • Echocardiogram
  • Auidometry - to check for hearing impairment.
  • Optometry

👀 Screening

All women are offered screening. Screening differs from testing. Screening decides which women should receive more invasive testing for a definitive diagnosis.

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Screening tests:

It is done in the first and second trimester of pregnancy. Older women are at greater risk of Down’s syndrome.

🥇 Combined test

Done at 11 - 14 weeks. It has 2 components:

  1. Ultrasound - measuring nuchel translucency. Fluid accumulates in the neck and nuchel thickness >6mm.
  2. Maternal blood test - there are 2 tests that are done:
    1. Beta-hCG - increases.
    2. Pregnancy-associated plasma protein-A (PAPPA) - decreases.
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Triple test - only involves maternal blood testing.

Performed at 14 - 20 weeks.

  1. Beta-hCG - increases.
  2. Alpha-fetoprotein (AFP) - decreases.
  3. Serum oestriol - decreases.

Quadruple test - triple test + inhibin-A.

Performed at 14 - 20 weeks.

  1. Beta-hCG - increases.
  2. Alpha-fetoprotein (AFP) - decreases.
  3. Serum oestriol - decreases.
  4. Inhibin-A - increases.
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🧪
Confirmatory testing:
  1. Chorionic villus sampling - as the name implies, we sample villus tissue from the placenta using ultrasound guidance. It can be done transcervically or transabdominally. It is done 11-14 weeks. Risk of miscarriage is 0.5-1%
  2. Amniocentesis - ultrasound guided aspiration of amniotic fluid. Done at 15-20 weeks. Risk of miscarriage is 1%.
  3. Non-invasive prenatal testing (NIPT) - tests maternal blood for foetal DNA. Fragments of foetal DNA pass into maternal blood from the placenta, and these can be analysed and karyotyped to assess for Down’s. However, it is not a definitive test.
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