Family History and Mendelian Inheritance

Question 1

Why take a family history?

Answer 1

-Establishes rapport between consultant and counsellor
-Demonstrates mode of inheritance of the particular disease in the family
-Provides information on family relationships with identification of other individuals who may be at risk
-Identifies consultant’s concerns and perceptions of the disease
- Aid in diagnosis
=Identify spectrum of illness/ medical diagnosis within family
=Demonstrates mode of inheritance of disease in family
=Identify those who are in best position for further investigation
-Identify those at risk of disorder

Question 2

What information needs to be collected on as many relatives as possible?

Answer 2

• Full name (including maiden name)
• Date of birth
• Date and cause of death
• Number of children and miscarriages
• Any specific medical diagnoses

Question 3

What are the types of Single Gene Inheritance patterns?

Answer 3

• Autosomal dominant

- X linked

Question 4

Describe Autosomal Dominant

Answer 4

• More than one generation involved
• Transmission of the disease from father to son (male to male transmission)
• Males and females affected with equal frequency and severity
• Neurofibromatosis Type 1

Question 5

Describe X-linked

Answer 5

• Usually only males affected
• More than one generation involved with the disease appearing to be passed on through normal females
• No male to male transmission
• Duchenne Muscular Dystrophy= progressive disorder, boys gradually waste muscle, chair bound, other complications
• Fragile X Syndrome

Question 6

Describe autosomal recessive

Answer 6

• One or more affected children with unaffected parents
• Usually only one generation involved
• Males and females affected with equal frequency and severity
• A higher incidence of consanguinity

Question 7

How to we calculate population carrier frequency in autosomal recessive disease?

Answer 7

Use Hardy Weinburg equation

p2 +2pq + q2 = 1

Where p = normal allele and q = disease allele

Question 8

What is Consanguinity?

Answer 8

Mating of blood relatives
Percentage of genes shared:
-First degree= 100 - 50%
-Second degree= 25% (one generation removed)
-Third degree= 12.5% (first cousins)

Question 9

What is Genetic counselling?

Answer 9

the process by which patients or relatives at risk of a disorder that may be hereditary are advised of the consequences of the disorder, the probability of developing or transmitting it and of the ways in which this may be prevented, avoided or ameliorated

Question 10

What is the terminology/ diagrams in family trees?

Answer 10

• Consultand= person coming to see you
• Proband= first person identified to have disorder
• Birth order (siblings)
• Male on left= square, female on right= circle

Question 11

What are the characteristics of autosomal dominant inheritance?

Answer 11

• Penetrance= affected person may or may not develop symptoms or show signs of the disorder (skipping a generation)
• Expressivity= variation in the clinical presentation/ phenotype between patients

Question 12

Describe Fragile X Syndrome

Answer 12

• 1:4000
• Commonest non-chromosome cause of mental retardation
• Mild to severe mental retardation
• Macroorchidism (post pubertal)
• Long face, prominent jaw, thick nasal bridge, large ears
• Joint hypermobility
• Autistic features, ADHD

Question 13

What is X-inactivation?

Answer 13

• Carrier females can be affected by X-linked disorders
• Consequence of the process called X-inactivation or Lyonization
• Random process
• If in an excess of cells, the normal X chromosome has been switched off then a female carrier of an X-linked disorder can be affected