Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Genetic counselling
What is GC?

History and
pedigree
construction

Clinical
examination
and
confirmation of
diagnosis

Risk assessment

Communication
and counselling

Discussion of
options

Back-up and
support

What is GC?
Sheldon Reed - coined the term in 1947 ------------ Original definition has evolved
 Harper – the process by which patients/relatives at risk of a disorder that may hereditary are advised of the
consequences of the disorder, the probability of developing or transmitting it and ways in which this may be
prevented, avoided or ameliorated
...

GC today… the process of helping people understand and adapt the medical, psychological and familial implications
of genetic contributions to disease
The process integrates:
1
...
Education about inheritance, testing, management, prevention, resources and research
3
...

Miscarriages, neonatal deaths, handicapped or malformed children and parental consanguinity information may not
be divulged unless specifically asked about
Usually not necessary to trace back beyond 3 or 4 generations (early medical details often inaccurate, and it’s
difficult to obtain beyond that)
Sometimes important to link kindreds to establish a common ancestor – genealogical records useful and a number
of sources are available in Europe
...

The pattern of any dm’s is usually more important than a single sign
Diagnosis aided by computerised databases

Some descriptive terms in dysmorphology

Standard DM measurements include: height, arm
span, weight, sitting height, interpupillary distance,
ear length, testicular volume, and head
circumference
Chromosome and molecular studies aid Dx, as well as referral to specialists in other fields such as neurology or
ophthalmology
...
g
...
(e
...
NTDs)
Empiric risks are influenced by the population incidence (HIGH and LOW risk areas), the relationship to the affected
individual, the number of affected individuals in pedigrees and sex if there is a sex difference in the population
frequency
...
g
...
g
...
g
...

Modified genetic risks
Are obtained by using (Reverend Thomas) Bayes theorem
...


This may be modified by posterior information, usually based on number of offpsirng
and/or the results of tests, allowing conditional probabilities to be determined
...
The
final probability for each event = its posterior or relative probability
Obtained by dividing the joint probability for the event by the sum of all the joint
probabilities
...
8
80% of heterozygotes express the condition in some way
...
4
What’s the risk reduction for the future child (lll1) of such a person?
Can use either a logical approach or Bayes’ theorum to calculate the risk of being affected

(“Although it holds true that for many disorders, risk assessment simply involves the provision of a
straightforward D or R recurrence risk, and that does still apply in some situations today, but increasing awareness
of the complexity and heterogeneity of genetic disease has focused attention on the importance of taking other
factors such as reduced penetrance and delayed age of onset, into account
...
Young, 2007, 3rd ed, oxford university press
...
8
Imagine 12 has 10 children, 5 on average will inherit the gene, and 4 of these will be
affected
6/10 will be unaffected, and 1 of these will carry the mutant allele, the other 5 the
normal allele
...
8
Consider all individual ll1 and how the risk
to her offspring lll1 is modified by the fact
that she is not affected herself
As before, probability that lll1 will inherit
the mutant allele and be affected is 1/6 x
½ xP = 1/15

AUTOSOMAL DOMINANT INHERITANCE
AD disorder with late onset e
...
Huntingtons disease

The son is healthy at age 50 years and wants to know the probability that his 10 yo daughter will develop HS in later
life
First necessary to calculate Bayesian risk for individual ll1 using the age of onset graph
Prior probability that his daughter lll1, has inherited the disorder is 1/3 x 1/2 = 1/6
AUTOSOMAL RECESSIVE INHERITANCE
With an AR disorder, the biological parents of an affected child are both heterozygous

Risk the each child is affected is ¼
The probability that a healthy sib of an unaffected individual is a
carrier is 2/3
...
Multiply the product of these 2 probabilities
by 1/4 to give the risk of a child being affected
If sister iii3 of the affected boy married her first cousin lll4, the
probability that their first child would be affected is 2/3 x ¼ x ¼ =
1/24
If she married an unrelated male – probability would be 2/3 x 2pq x ¼
For CF in the UK, 2pq is ~1/25 so the final risk of having an affected child would be 2/3 x 1/25 x 1/4 = 1/150
Screening for the most common mutations in CF detects ~90% of all carriers of Western European origin
Thus the probability that this healthy member of
the population is a carrier has been reduced from
1/25 to 1/241

X-LINKED RECESSIVE INHERITANCE

Conditions usually transmitted by healthy female carriers to their male offspring
When only 1 affected son, may be the result of a new mutation or gonadal mosaicism, as well as being inherited
from a carrier female
Risk calcuations often complicated
Additional information may be obtained from biochemical tests or the use of linked DNA markers
With biochemical tests, often an overlap between control values and those from known carrier females
...
The 2 situations
cannot always be reliably distinguished
...

Risks in context
Specific risks may be additional to general population risks thus must
be placed in context
...
In promoting a patient’s best interest, the assumptions of both the
patient and the provider must be held up for examination and discussed in the attempt to arrive at a consensus
...


Reflecting on the cultural nature of biomedicine’s ideas about risk, disability, and normality helps us to realize that there are many valid interpretations of what
is in a patient’s best interest
...
Overall, this helps to improve the quality of care-Bhogal & Brunger 2010!

Information to be conveyed may include:
Clinical features (average and range), complications, natural history, prognosis and treatment/effective
management, genetic basis, recurrence risk and general populaiton risks
Feelings of guilt/stigmatisation may need to be allayed
Common misconceptions about heredity may need to be dispelled
Discussion of options







Reproductive options can then be discussed
Counselling has to be non-directive and comprehensive
Fears may be unjustified and the couple can go ahead with pregnancy with reassurance of no increased risk
If there is an increased risk, and the disease burden is significant , other options must be considered
If PND is available and termination acceptable, couple may go ahead with pregnancy
If termination of fetus is not acceptable, may decide on no further pregnancies (ensure adequate
contraception) or consider further possibilities such as AID, egg donation, adoption, or IVF with
preimplantation diagnosis

Factors affecting reproductive decisions

Follow up and support
Consultands may need 1+ SESSION
A FOLLOW-UP LETTER may be sent SUMMARISING the
information & offering the facility to return if they have
new questions
Information often distressing so should be options
available for LONG-TERM SUPPORT
GENETIC REGISTERS enable consultands to be contacted
when new opportunities arise such as improved
carrier/prenatal tests
Patient SUPPORT GROUPS now widespread and offer
support and companionship

Outcomes







Most medical activities have quantifiable end points such as infection rates, survival after surgery etc
Defining outcomes in genetic counselling more difficult
...

In practice, 3 main outcomes have been assessed ………………1) Recall…………
...




---