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

Epidemiology and risk factors

Answer 2

• Advanced maternal age
• Carriers of the genetic translocation for DS
• Previous child with DS

Question 3

Signs

Answer 3

Facial:
- Brachycephaly
- Flat occiput
- Epicanthal folds
- Upslanting palpebral fissures
- Short nose with low nasal bridge
- Small ears
Oral:
- Small mouth
- Large protruding tongue
Neck:
- Short neck
- Excess skin posteriorly
- Neck pain: atlantoaxial instability
Hands:
- Short hands
- Single palmer crease
- Fifth finger clindodactyly
Feet:
- Sandal toe gap: between 1st and 2nd toes
Eyes:
- Brushfield spots
- Congenital cataracts
Neurology:
- Hypotonia
GI:
- Duodenal or anal atresia
- Duodenal or anal stenosis
Cardiovascular:
- Heart murmur - AVSD

Question 4

Symptoms

Answer 4

Developmental delay:
- Gross motor delay
- Language delay
- Feeding difficulties
Cognitive:
- Learning difficulties
- Autistic spectrum disorders
ENT:
- Recurrent otitis media
- Hearing loss: secondary to chronic infection
GI:
- Constipation

Question 5

Antenatal screening for Down’s syndrome

Answer 5

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. (before 15 weeks).
= Amniocentesis = USS guided aspiration of some amniotic fluid using a needle and syringe (15-20 weeks) .
- Mother’s choice if she wants to do it.
Older women have higher risk of Down’s syndrome

Question 6

Diagnosis

Answer 6

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 7

Maternal blood test’s

Answer 7

• 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 8

Triple test

Answer 8

• 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 9

Quadruple test

Answer 9

• 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 10

Non-invasive prenatal testing

Answer 10

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 11

Treatment

Answer 11

• 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 12

Routine investigations

Answer 12

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

Question 13

Prognosis

Answer 13

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

Question 14

Complications

Answer 14

• 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