Medical, Genetic and Social Aspects of

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Medical, Genetic and Social Aspects of
Huntingtons Disease Dr Sheila A
Simpson Clinical Genetics
Aberdeen
March 23rd 2007
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What is Medical Genetics?
Cytogenetics Scientists who examine chromosomes
the karyotype Molecular Genetics Scientists who
examine chromosome structure DNA Clinical
Genetics Doctors who specialise in inherited
disorders
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Chromosomes, Genes and DNA
Gene
Cell
Chromosomes
Protein
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Clinical Geneticist A doctor who specialises
in inherited diseases
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Men are not going to embrace eugenics. They are
going to embrace the first likely trim-figured
girl who comes along, in spite of the fact that
her germ plasm is probably reeking with
hypertension, cancer, haemophilia, colour
blindness, hay fever, epilepsy, and amyotrophic
lateral sclerosis
Logan Glendening(1884-1945)

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Clinical Features

• Movement Disorder
• chorea
• 
  athetosis
• 
  myoclonus
• 
  rigidity
• FIDGETY

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Clinical Features

• Personality changes
• irritable
• 
  apathetic
• loss of
  empathy
• self
  centred
• 
  disinhibited
• A different person

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Clinical Features

• Psychiatric Disease
• depression
• paranoia
• psychosis

Major features less common
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Clinical Features

• Cognitive Changes
• poor
  planning
• poor short
  term memory
• lack of
  insight
• Subcortical dementia leading to poor executive
  functioning

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Clinical Features

• First signs around late 30s early 40s
• .but variable
• Can live 15 to 20 years until death due
• to bronchopneumonia or head injury

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Prevalence

• 5-7/100,000 - 14/100,000
• 700 people affected by HD in Scotland NOW
• 5 x that number at 50 risk
• 10 x that number at 25 risk
• Double that figure for partners and carers
• THIS IS NOT A RARE DISEASE

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Autosomal Dominant Inheritance

• Men and women affected
• Each child has 50 chance of inheriting the
  mutation
• Only those who have the gene can transmit it

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Genetics

• The gene is known (1983)
• The mutation is known (1993)
• Diagnostic, predictive and antenatal
• tests are available

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The Gene IT15 Mutation CAG
repeat sequence
polyglutamine disorder DNA
expansion
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The Huntingtons Gene


DNA triplet
CAG triplet
Normally up to 35 repeats gt than this is
diagnostic of HD
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Presymptomatic Predictive Testing

• psychological, social, economic and family
  dynamic
• risks should be explained

• personal implications of genetic information
  should
• be discussed

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Ethics in Medicine

• Respect for autonomy
• (including protection of those with diminished
  autonomy)
• Beneficence
• Non-maleficence
• Justice
• (fairness, equity, distributing the benefits
  and burdens of healthcare fairly in society)

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Prediction and uncertainty

• Test information must be usable for prevention or
  treatment
• Susceptibility testing requires adequate
  information about uncertainty
• Predictive testing requires proper counselling
• Children or adolescents should only be tested if
  there are potential medical benefits
• Third parties (employers, insurers) should have
  no access

WHO Guidelines on Ethical Issues in Medical
Genetics
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Ethical Issues in Medical Genetics
Shared Genetic Heritage (autonomy???)

Genetic disease affects families, not
individuals Discovery
of a genetic disorder implies a risk for
relatives Storage of information and samples
(justice???)
Genetic information and the
genetic register Prediction of disease (non
maleficence???)
Gene mutations may confer a
risk or certainty of future disease
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The Good the Bad and the Ugly
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and Margaret
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The Genome Generationgrowing up at risk of
late-onset familial disease

• Karen Forrest
• Sheila Simpson
• Edwin van Teijlingen
• Zosia Miedzybrodska
• Lorna McKee
• Funded by The Wellcome Trusts Programme in
  Biomedical Ethics

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Impact of HD on family dynamics

• Parenting/child-centred risk
• Changes in care giving roles e.g. young carers
• Changes in family membership e.g. not belonging,
  family rifts
• Patterns of communication secrets, layers of
  knowing, when to tell the children?
• Preselection collude in denial of symptom onset
  induce suicide of affected person

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Project Aims by Qualitative Interview

• To explore YPs views and experiences of growing
  up with familial diseases like HD
• e.g. their understanding of inheritance,
• risk perception, attitudes to genetic
  testing, reproduction, coping strategies, caring
  activities, family relationships and
  communication

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Growing up with HD a lonely predicament?
they act like children, mood swings, loadsa
arguments in your hoose it makes you nuts it
tears your family apart half the family dont
speak to one another I just get really angry,
you probably noticed theres a hole in the
door theyre not offering help and you feel
like you can speak to no-one
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Results

• Children and YP are not always damaged, but often
  are
• YP want to speak with a neutral person outside
  the family - value of YPs HD worker
• Leave the door open

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This man has Huntingtons disease - I have not
arranged to see him again, there is nothing more
I can do.
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A pathway of care??
Diagnosis Death
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We have to ask ourselves whether medicine is to
remain a humanitarian and respected profession or
a new but depersonalised science in the service
of prolonging life rather than diminishing human
suffering. Elisabeth Kubler-Ross American
Psychiatrist ..quoted
in the British Medical Journal, 6 August, 2005
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Assessment

• Neurological examination
• Neuropsychology
• Swallowing assessment
• Speech and language
• Occupational therapy assessment

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Management

• Identify depression
• obsessive disorder
• behavioural problems
• irritability
• Medical problems
• weight loss
• chest infection
• THESE CAN BE TREATED

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Management

• Home environment
• .. being alone / smoking
• .. stairs / cooking / eating
• Finances who is in control?
• ..benefits/exemptions
• ..competency

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Management
Information for affected individuals, carers
and families

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Management

• Movement disorder
• ..are drugs necessary?

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Management

• Co-ordinated management within hospital
• and community

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Informed management
preservation of skills
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Leads to..
Care at home in community for longer
Reduced crisis management
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Neuropsychology impairment in range of
cognitive functions with slowing of information
processing
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Planning ahead involves ....
advanced directives ..are they
physically or mentally incompetent? Neuropsycho
logy assessments as part of routine management
can define stage
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We must learn to be less arrogant and less
controlling as a profession and allow patients
more autonomy Lesley A M Evans Former
Consultant Geriatrician, BMJ, 11 June, 2005
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End of Life Assessment of
competency Finances, driving,
treatment decisions Planning leads to
Empowerment of the patient
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Sweating the small stuff
for Keith
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