Genetics - Down Syndrome

Question 1

Definition

Answer 1

Three copies of chromosome 21 = trisomy 21 = gives characteristic dysmorphic features and is assosciated with a number of assosciated conditions they have vary between individuals.

Question 2

Dysmorphic features

Answer 2

• Hypotonia (reduced muscle tone)
• Brachycephaly (small head with a flat back)
• Short neck
• Short stature
• Flattened face and nose
• Prominent epicanthic folds
• Upward sloping palpebral fissures
• Single palmar crease

Question 3

Epicanthic folds definition

Answer 3

Folds of skin covering the medial portion of the eye and eyelid. The palpebral fissures are the gaps between the lower and upper eyelid.

Question 4

Antenatal screening for Down’s syndrome

Answer 4

All women are offered screening for Down’s syndrome:
- Aim is to decide if women should recieve more invasive tests to give definitive diagnosis if risk greater than 1/150 (5%):
= Chorionic villus sampling (CVS) = USS guided biopsy of the placental tissue. This is used when testing is done earlier in pregnancy (before 15 weeks).
= Amniocentesis = USS guided aspiration of some amniotic fluid using a needle and syringe. This is later in pregnancy once there is enough amniotic fluid to make it safer to take a sample.
- Mother’s choice if she wants to do it.
Older women have higher risk of Down’s syndrome

Question 5

Diagnosis

Answer 5

FIRST LINE = Combined test
- Most accurate and test of choice where possible
- This test is performed between 11-14 weeks gestation
- Involves combining results from USS + maternal blood tests
- USS measures nuchal translucency = thickness of the back of the neck of the fetus = Down’s causes a nuchal thickness over 6mm

Question 6

Maternal blood test’s

Answer 6

• Beta‑human chorionic gonadotrophin (beta-HCG). A higher result indicates a greater risk.
• Pregnancy‑associated plasma protein‑A (PAPPA). A lower result indicates a greater risk.

Question 7

Triple test

Answer 7

• Performed between 14 and 20 weeks gestation. It only involves maternal blood test results:
• Beta-HCG. A higher result indicates greater risk.
• Alpha-fetoprotein (AFP). A lower result indicates a greater risk.
• Serum oestriol (female sex hormone). A lower result indicates a greater risk.

Question 8

Quadruple test

Answer 8

• The quadruple test is performed between 14 and 20 weeks gestation.
• It is identical to the triple test but also includes maternal blood for inhibin-A.
• A higher inhibin-A indicates a greater risk.

Question 9

Non-invasive prenatal testing

Answer 9

Non-invasive prenatal testing (NIPT) is a relatively new test for detecting abnormalities in the fetus during pregnancy. It involves a simple blood test from the mother. The blood will contain fragments of DNA, some of which will come from the placental tissue and represent the fetal DNA. These fragments can be analysed and detect conditions such as Down’s.

NIPT is not a definitive test, but gives very good indication of whether the fetus is affected. This is gradually being rolled out in the NHS as an alternative to invasive testing (CVS and amniocentesis) for women that have a higher than 1 in 150 risk of Down’s syndrome.

Question 10

Treatment

Answer 10

• Occupational therapy
• Speech and language therapy
• Physiotherapy
• Dietician
• Paediatrician
• GP
• Health visitors
• Cardiologist for congenital heart disease
• ENT specialist for ear problems
• Audiologist for hearing aids
• Optician for glasses
• Social services for social care and benefits
• Additional support with educational needs
• Charities such as the Down’s Syndrome Association

Question 11

Routine investigations

Answer 11

Regular thyroid checks (2 yearly)
Echocardiogram to diagnose cardiac defects
Regular audiometry for hearing impairment
Regular eye checks

Question 12

Prognosis

Answer 12

Prognosis varies depending on the severity of the associate complications. The average life expectancy is 60 years.

Question 13

Complications

Answer 13

• Learning disability
• Recurrent otitis media
• Deafness: Eustachian tube abnormalities lead to glue ear and conductive hearing loss.
• Visual problems such myopia, strabismus and cataracts
• Hypothyroidism occurs in 10 – 20%
• Cardiac defects affect 1 in 3, particularly ASD, VSD, patent ductus arteriosus and tetralogy of Fallot
• Atlantoaxial instability
• Leukaemia is more common in children with Down’s
• Dementia is more common in adults with Down’s