Download Presymptomatic Diagnosis

Ethic and Genetics
Pr. Didier LACOMBE
Head Dept. Medical Genetics
National Reference Center for Birth Defects
CHU de Bordeaux
Université Bordeaux 2
IV° French-Chinese Bioethics Conference
Bordeaux 8-9/04/2010
Department of Medical Genetics
Roles : diagnosis of a genetic disease
And what’s around the diagnosis :
- Care of the patient, familial support
- Genetic counseling
- Familial screening
- Prenatal diagnosis
- Presymtomatic diagnosis
Medical Genetics = Family involvement
Genetic Counseling
Information of proband and family :
* Disease characteristics : natural history, features,
evolution, complications...
* Heredity (mode of inheritance)
* Recurence risk
* Genetic testing possibilities
* Screening and prenatal diagnosis possibilities
Familial Screening
• Screening for heterozygous status of recessive or
X-linked conditions (mostly)
• Affected child
Familial cascade screening
• Transmission of information via patient/family,
not via doctors to concerned persons (avis 76 du comité
consultatif national d’éthique pour les sciences de la vie et de la santé)
• Information via Biomedical Agency (letter) ?
Familial Screening
• Informed free consent (Code de la Santé Publique Art. R1131-5)
• No discrimination because of genetic
characteristics (Code Civil - Art. 16-13)
• No insurance or work implications, no
obligation of genetic testing (Code de la Santé
Publique - Art. 1141-1)
Prenatal Diagnosis (PND)
• Positive family history and gene mutation
identified (~ 2000 disease-causing genes)
• Risk → Knowledge (affected or not)
• France: PND for severe and non treatable
diseases at the time of diagnosis
• Genetic counseling visite before PND (article
L.2131-1 du code de la santé publique)
• Final decision to parents for medical abortion
Prenatal Diagnosis
• In France PND via Multidisciplinary
Centers agreed by Agence de Biomédecine
• Medical abortion legal up to the end of the
pregnancy
• Decision from the couple
• Psychological support
Preimplantatory Diagnosis (PIP)
• Genetic testing on 1/2 cells before uterus
transfert of healthy embryos
• Avoiding of potential medical abortion (MA)
• Couples with multiples MAs
• Indication of in vitro fecondation
• PND/PIP: acceptability for late-onset genetic
diseases ? (cancer predisposition …)
Presymptomatic Diagnosis
• Definition (P.Harper, 1997) = situations
where an abnormal result indicates that the
disease will almost develop at some point in
life.
• New Genetic Medicine:
- High risk asymptomatic persons (~ 50%)
for genetic disease
- Late-onset disorders
- Monogenic mendelian disorders
Presymptomatic Diagnosis
• Knowledge of genetic status of
asymptomatic individuals at risk for
developing an identified genetic disorder
• Concerned persons :
- at risk
- adults
- asymptomatic (absent features)
- volontary consent
Presymptomatic Diagnosis
• Key notion of medical benefit
• 2 different situations :
• - Possible preventive/curative treatment
(ex: cancer predisposition)
• No preventive/curative treatment available
(ex: neurodegenerative disorders)
Model = Huntington disease
Presymptomatic Diagnosis
Ethical principles (WFN, Neurology, 1999) :
• Benefit
• Adulthood (independence)
• Freedom
• Engagement
• Confidentiality
• Equality
• Right of not-knowing
Presymptomatic Diagnosis
• France (Décret 2000-570) : conditions of
prescription of genetic testing
• Multidisciplinary teams (Ministry of Health)
HD: geneticist, neurologist, psychologist
• Care and testing (4-6 months) protocols
• Illegal in children without medical benefit
Presymptomatic Diagnosis
Justifications
•
•
•
•
•
To relieve uncertainly about genetic status
To plan a family
To plan for the future
To inform the children
To be sure one is carrier
54 %
14 %
13 %
14 %
2%
Presymptomatic Diagnosis
Remarkable events
• Pregnancy
(50 % PND; 50 % MA)
20 %
• Serious adverse events:
- Psychological distress and depression 9 %
- Psychiatric hospitalization
2%
- Suicide attempt
0%
Presymptomatic Diagnosis
Conclusions
• New concept
• Molecular genetic advances :
activity
• 2 care levels:
- Severe diseases : HD model
SCA, hereditary dementia/Alzheimer
- Mild diseases :
CMT, FSH, myotonic dystrophy
Genetic Testing in Children
• Information, free choice, consent : not possible in
children, choice of the parents
• Possible in symptomatic children (CF, DMD ..)
• Possible: medical benefit in asymptomatic child:
- curative/preventive treatment: cancer
predisposition syndromes (APC, Gorlin …)
- screening/follow-up (Steinert, glaucoma …)
- professional/social orientation (CM, CMT …)
Genetic Testing in Children
Genetic tests forbidden in asymptomatic child :
• Severe late-onset genetic disorders
- Hereditary cancer predisposition (BRCA1,
BRCA2, HNPCC …)
- Neurodegerative late-onset diseases (HD, SCA,
CADASIL …)
• Recessive heterozygous status
• Multigenic/polyfactorial heredity
Genetic Testing in Children
• Personal benefit for the child
• Preventive/curative treatment for the family
• Deprivation of the right of not-knowing
• Breakdown in the child-parents relationship
• Disease anticipation
Prescription of genetic testing:
Difficulties
• Lack of specific information before
clinical use (genetic counseling)
• Random genetic predisposition identification
(CGH-array and cancer predisposition)
• Presymptomatic testing
• Minor children
• No individual medical follow-up
Free access to genetic testing
(autotests via internet)
• No medical follow-up
(indication, interpretation ..)
• No medical indication/interest
• No ethic or juridic guide
(identity, consent, child ..)
• No technical guide
(fiability, quality ..)