Download The Genetic Counseling Outcome Scale

Provision of Genetic
Counselling for Patients with
Retinal Dystrophy
Prof. Graeme Black, Ms Georgina Hall
Depts. of Ophthalmology and Clinical Genetics,
Manchester
Causes of childhood blindness

Developed countries
30-50% childhood visual handicap is genetic

Developing countries
Africa
Genetic
S America
India
21%
30%
30%
Intrauterine
7%
2%
10%
Perinatal
Childhood
2%
34%
2%
37%
20%
12%
Unknown
35%
30%
27%
In developed countries,
hereditary causes of blindness
are the most important cause of
childhood visual handicap
Retinitis
pigmentosa
 Symptoms
• night blindness
• constriction of peripheral
visual field
• later loss of central vision.
 Diagnosis
• Progressive photoreceptor
dysfunction
• undetectable / reduced ERGs……
rod-mediated responses more
severely affected than conemediated (i.e. rod-cone dystrophy).
 Retina
• pigment in bone-spicule distribution.
Retinitis pigmentosa

1 in 2500

Genetic condition

Caused by single
fault in one gene
Deoxyribonucleic
acid (DNA) and
chromosomes
46 chromosomes
 Human chromosomes
carry 20,000 to 30,000
genes

Genes and Inheritance

Chromosomes
–
–

22 identical pairs
(“Autosomes”)
1 pair non- identical
(“Sex Chromosomes”)
XX=Female XY=Male
Each chromosome carries
1 copy of gene
(ie 2 copies of a
gene per pair)
What is a gene?
Gene
Protein
A genetic disorder is caused by
a single faulty gene
Classification of RP

Genetic
–
–
–
–

Autosomal dominant
X-linked
Autosomal recessive
Sporadic
10-15%
5-15%
30-50%
20-50%
Onset
– Birth : Leber congenital amaurosis
– Childhood : many X-Linked, AR forms
– Later onset: some AD forms

Retinal manifestations
(Symptoms or ERG define)
– Cone-rod dystrophy
– Rod-cone dystrophy
– Cone dystrophy
– Rod dystrophy
Genes and RP

Confusing
– Faults in a large number of genes can cause
RP and retinal degeneration
Retinal dystrophies

Hugely variable
– onset
outcome
retinal findings
– gene defect
inheritance pattern

Gene analysis tells us there are a large
number of different forms - ?100 -200

Majority unclassifiable clinically

Increasingly the precise genetic defect is
known for many retinal degenerations…… or
rather could be known
Genetics and Ophthalmology
in Manchester
– 8 clinics per month
– Run by clinical genetics alongside
ophthalmology
– Coworkers present
– Held in clinical genetics unit / eye hopsital
– 4-6 pts/clinic
• Time
• examine family members
– Letters to patient
Why have a genetic
ophthalmic clinic at all?

Large group of uncommon disorders
– Unified approach
– Diagnosis
– Investigation
– Counselling / FH Issues

Pts referred for specialist opinion
– ?correct diagnosis
– ?geneticists cannot examine
Clinician’s Objectives

Diagnosis

Risk estimation to family members
Screening requirements
 Information
 Support

Patient’s objectives (I think….)

Treatment

Prognosis
Understanding
 Risks to family members (Children)

– Prenatal diagnosis

Presymptomatic diagnosis
Perhaps our objectives are different….
Genetic Counsellors
MSc genetic counselling
 Nurses

– Additional training in genetics and
counselling
300 in the UK
 Professional body (AGNC)
 Register (GCRB)

– Code of ethics / conduct
– Competency assessment
What is “genetic counselling”
Communication process
Comprehend medical information
Appreciate the hereditary impact
Facilitate decision making (genetic
testing, reproduction) in context of beliefs
/ family / cultural sensitvity
Make best possible adjustment to
genetic condition in family
Why do people request genetic
counselling?
Diagnosis
 What is the cause?
 What will it mean for me?
 What are the risk to my children (other
family members)
 What screening / tests / treatments
available

Nature of genetic information
Patients may need to absorb a lot of
new information that is often complex,
abstract and difficult to grasp.
 Rapid advances in understanding of
genetic basis of eye conditions.
 Heterogeneity – inheritance not clear
cut.

Counselling issues
Over and above emotional impact of
visual impairment (grief, loss)
 Burden / guilt
 Coping with risk / uncertainty
 Difficult decisions
 Impact on relationships / family
dynamics
 Family coping styles / beliefs around
visual impairment

X-linked retinitis pigmentosa
Boys affected late childhood / early
teens
 Progressive
 No treatment
 Faulty gene on X chromosome
 Mothers are “carriers”

– Half daughters will be carriers
– Half sons will be affected
XL Retinitis Pigmentosa
3
5
3
L dropped out of school, no exams
 Diagnosed XLRP aged 17
 Anger and depression
 Isolated

M denied diagnosis. “It hasn’t come
from me”
 ?guilt

XL Retinitis Pigmentosa
3
5
guilt
3
S
Am I a carrier?
Sister S wanted to know if she was a
carrier
 New baby son J
 How would she feel if she were a
carrier?
 How would she feel about her new
baby?
 Would it affect decisions about further
pregnancies?

XL Retinitis Pigmentosa
3
5
3
L
S
J
Testing children?
J has a 50% risk of being affected?
 Should he be tested?
 Would it affect parenting / schooling?
 Benefits to S – relieving uncertainty
 Benefits to J?

Meeting other family members
Individual needs / decisions
 Confidentiality
 Counselling issues evolve with time

Norrie’s disease
X-linked
 Blind at birth
 Additional risks

– 1/3 boys have learning difficulties
– 1/3 boys develop deafness
Norrie disease
Chromosome 11p11.4
NDP gene
Whole deletion incl
Neighbouring MAO-A/B
Family
Tom
Shock
 It’s my fault
 How will I cope / my family

Sister about to start IVF treatment
 Burden of informing sister

Sister
50% chance she is carrier
 Able to offer a blood test
 Options

– Decide not to have a pregnancy
– Continue with IVF (7/8 chance baby would
not have Norrie’s) or test a pregnancy
– Have pre-implantation genetic diagnosis
Outcomes
Sister not a carrier, able to continue with
IVF without anxiety
 Tom doing extremely well. No learning
difficulties or hearing problems. Very
dedicated parents.
 Future concerns that daughter could be
a carrier. Will not offer testing until she
can make her own choice.

Genetic testing for diagnosis:
Can it be done?

Genes identified for wide
range of retinal
dystrophies are known

Genes able to be
sequenced
http://www.sph.uth.tmc.edu/Retnet/sum-dis.htm#D-graph
Molecular Genetic Testing
DNA sample (peripheral blood)
 Affected Individual / Obligate carrier


Identify sequence variant
– not present in normal population
(monogenic disease)
– In gene known to cause retinal disease
What is the Position in 2011?
Technological Advances mean tools
more powerful than ever
Many laboratories now offer
diagnostic testing to the NHS
http://www.mangen.co.uk/molecular_eye_and_rare_disease.asp
adRP
Genetic testing for retinal
dystrophies is possible and available
However testing is not universal
Where it is clearly required,
testing is usually available
N = 1131
xlRP
Why do patients require testing?
Is the case for genetic testing
persuasive?
What is the evidence base?
n = 840
Why develop genetic eye
services?
Inequity of services
 Gene discovery
 Patient demand
 Treatment trials

Research to improve services
Regard study
 Programme Grant

Communication, accessibility
 Developing services for genetic
counselling and testing

Improving accessibility
Hospital appointments by phone,
email
 Written information – large print,
email, braille, audio transcription
 Tactile genetic diagrams
 CCTV / software enlargement of
diagrams

Developing counselling
services
Mainly anecdotal evidence of
counselling needs of families with
inherited eye disease
 Requires robust research
 Evidence based
 MRC Framework for developing a
complex intervention

MRC framework

Phase 1
– Modelling the intervention
– Components

Phase 2
– Exploratory trial

Randomised control trial
Aims
Design a patient led care model for
counselling and testing
 Develop evidence of patient benefit and
“value” of improved counselling

Phase 1
“Modelling”
 Qualitative interviews with families and
healthcare professionals
 Snowballing
 Grounded theory

PPI
Important to involve patients / users in
design, analysis and dissemination of
research
 Regard Patient Advisory Group

– Patients / users / experts
– Leading charities (RNIB, BRPS, Guide Dogs,
Macular Disease Society, NCBS, Genetic
Alliance)
– Patients
– VI researchers and social workers
PAG



Regular meetings
Formal presentations (teaching, training, updates)
Small group work
– Design methods



Informal discussion
Modify / improve design
Regular email contact / updates and queries
– E.g. Review of patient information prior to Ethics
application
– Publication of outputs included longer, more frequent
meetings
Advantages of patient
involvement



Motivation, extending knowledge base
Relationships with pt support groups
Focus work on improving patient care
– National patient perspective
– Timely, fitting with patient needs

Collaboration
– Genetic Alliance Route Maps, UK Vision strategy
workshop
Measuring benefit of genetic
counselling
Outcome measures
Information recall
“satisfaction” survey
Depression / anxiety
Genetic Empowerment scale
– Feelings around the condition, impact
on family, hope for future,
empowerment to make decisions
McAllister M et al, The Genetic
Counseling Outcome Scale: a
new patient-reported outcome
measure for clinical genetics
services Clinical Genet. 2011.
Phase 2

Exploratory trial
– Feasibility of intervention
– Pilot outcome measures / develop
estimates of effect size

Economic “value”
– Willingness to pay
– Economic modelling to understand cost
benefits of genetic testing
Conclusions


Retinal dystrophies important cause of VI in
children/ young adults
Emotional need related to
– VI
– Family / genetic / treatment needs



Services patchily delivered
Links to community support need to be
improved
Research into delivery and impact required