Genetics

Question 1

What are the reasons for referral to genetics?

Answer 1

• Family history of a genetic condition
• Dignosis of genetic conditions
  
  • Both known/unknown
• Managment of genetic conditions
• Genetic Counselling
  
  • aiding decision making
  • increasing understanding

Question 2

What do people need to know before undergoing a genetic test?

Answer 2

• What test is for / whats the point in having it?
• How likely is it to be positive?
• What happens if its positive?
• What happens if its negative?
• What if false positive/ false negative?
• Implications for other family members if positive result
• DNA storage - this is routine but patients need to be aware.

Question 3

What are the 2 main subtypes of genetic pregnancy testing / screening?

Answer 3

• Targetted - individuals with established risk of genetic disorders.
• Whole population - screening for the more commonly seen genetic disorders.

Question 4

What different DNA can be looked at in genetic testing?

Answer 4

May look at big chunks of dna (chromosomes) , or even the sequence of DNA itself too.

Question 5

What are the reproductive choices for parents who’s child will have a risk of genetic disease?

Answer 5

• Do nothing - test at birth
• Chorionic villus sampling / Amniocentesis
• Pre-implnatation genetic diagnosis
• Adoption - as a complete altnerative.
• Gamete donation - surrogacy
• Non invasive prenatal diagnosis/testing

Question 6

Invasive testing in pregnancy is associated with a risk of what?

Answer 6

Miscarriage.

Question 7

What is non-invasive prenatal testing (NIPT)?

When is it used?

Why may there be errors?

Answer 7

• NIPT - Prenatal screening test, can be done from 10th week of pregnancy.
• Small fargments of the foetal DNA from the placenta is free in the mothers bloodstream.
• This DNA is analysed for abnormalities.

Used in defined circumstances (mostly private) - planned to be test of choice in T21.

May be errors as the mothers DNA will be present there too.

Question 8

What are the various factors involved in the screening of Down’s Syndrome?

Answer 8

• Maternal age
• Triple screening - blood test that measures three things called alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol.(looking for defects)
• CUBS screening - combined ultrasound and biochemical test
• Selection for amniocentesis
• Free foetal DNA
  
  • Private currently

Question 9

Generally outline cystic fibrosis.

(defect, associated implications, diagnosis)

Answer 9

• Defect of cellular chloride transport.

Associated Defects​

• Meconium ileus - bowel obstruction due to increaingly thick meconium in the bowel.
• Increased lung infection incidence
• Pancreatic insufficency

Diagnosis

• Immunoreactive trypsin - elevated in CF
• Sweat Test - measures Cl- ions in sweat (elevated in CF)

Question 10

Generally outline Sickle cell disorders.

(gene abnormality and result, common symptoms, Screening)

Answer 10

• Inherited disorder affecting the HB gene, causing RBC to become sickle shaped.
• This can cause pain, tissue damage, infection and even death.

Screening

• SCD screening can identify carriers, allowing them to be counselled prior to pregnancy.

Treatment early in the disease can imrove the health of babies and prevent death.

Question 11

What is Tay-Sachs Disease?

(what it is, impact on child, prevalent in what groups)

Answer 11

• Progressive, genetic, lysosomal storage disease - due to a Hex A deficiency resulting in a build up of lipids, especially in the nerve cells of the brain.
• Baby usually develops normally until about 6 months of age. Progresive neurological deterioration. Usually fatal by 3-5 years.
• 1 in 25 Ashkenazi Jews and 1 in 250 of the general population are carriers.

Question 12

What screening do we carry out to newborn children?

Answer 12

Clinical Examination

Hearing test

Blood Spot

Question 13

Why do we screen babies?

Answer 13

• To enable early detection of pre-symptomatic babies. - epecially in at risk babies
• To enable early treatment to improve health - find the disease prior to development of symptoms. early treatment can improve the health of babies esp in conditions such as PKU and CHT (congenital hypothyroidism).
• To reduce anxiety caused by uncertainty over symptoms before clinical diagnosis is made.

Question 14

What are the major disease that are screened for in a newborn screening?

Answer 14

• Phenylketonuria (PKU)
• Congenital Hypothyroidism (CHT)
• Sickle Cell Disorder (SCD)
• Cystic Fibrosis (CF)

Question 15

Outline PKU

Answer 15

• Affects approximately 1 in 10,000 babies in UK (ie about 80 born each year)
  
  • Recessive condition – biochemical screen - carriers not identified
• Babies with condition are unable to break down phenylalanine (an amino acid in protein)
• Untreated babies develop serious, irreversible, mental disability
• Early treatment with a strictly controlled diet prevents disability
• Treatment should start by 21 days of age

Question 16

Outline CHT

Answer 16

• 1 in 4,000 babies UK
• 1 in 10 cases inherited – hormone test
  
  • carriers not identified
• Not enough thyroxine
• Untreated babies -> serious, permanent, physical and mental disability
• Early treatment with thyroxine tablets prevents disability
• Treatment should start by 21 days of age

Question 17

Outline Medium chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

Answer 17

• 1 in 10,000-20,000 UK babies
• Recessive inherited condition – carriers not identified
• Babies with MCADD cannot easily break down fat to make energy for the body
• Serious life-threatening symptoms can occur quickly in babies not feeding well or unwell
• Mean age at first presentation is14 months. 25% mortality rate
• Treatment to prevent metabolic crisis: avoid fasting and monitor frequency of meal
• Emergency regime: glucose polymer (maxijul) and IV dextrose