The Clinical Perspective

1. The Clinical Perspective Kerry Seitz Educator in Clinical Genetics & Principal Genetic Counsellor

2. The Clinical Perspective • The clinical genetics service • Role of Clinical Genetics Service • Role of Genetic Counsellor • Types of Patients Seen • Referral Sources to Clinical Genetics • Predictive Testing • Genetic testing in Children • Case studies.

3. The Clinical Genetics Service Involves close collaboration between: • Clinical Genetics service • Cytogenetics laboratories • Molecular Genetics laboratories • Other medical departments & colleagues, including primary, secondary and tertiary care. Note: These can be local or national, even international collaborations.

4. Role of Clinical Genetics • To diagnose/confirm a genetic condition • To assess referred patients’ & relatives’ level of risk of a genetic condition • To provide required information • To provide psychological support • To make recommendations re. surveillance • To make referrals to the MDT for management and treatment.

5. Role of Genetic Counsellor • Establish contact with the patient/family • Obtain medical history & family history • Identify issues important to individual/ family • Facilitate non-directive genetic counselling • Provide information autonomously or in conjunction with Geneticist • Provide support, including L/T contact –as needed. Aim: To enable those who seek information to reach their own fully informed decisions.

6. Referral Sources • GPs • Paediatricians • Midwives, Obstetricians & Gynaecologists • Oncologists & Cancer FH Clinics • Neurologists • Orthopaedics, Dermatologists, ENT • Genetic Laboratories & other Clinical Genetic departments.

7. Types of Patients Seen • Those with a family history of a genetic condition. • Those who have a suspected genetic condition themselves. • Those with a strong family history of cancer. • Pregnant couples/women. • Children with multiple problems (eg. dysmorphism, developmental delay, learning difficulties).

8. Predictive and Presymptomatic TestingThis is usually carried out when a patient is at 25% or 50% risk of having inherited the familial mutation.

9. Rationale for Performing Predictive Testing • To remove uncertainty. • To obtain clarification of gene status (ie. Gene change carrier/non-carrier). • To ensure appropriate screening is arranged (ie. if gene change carrier). • To obtain clarification of risks to children. • To provide information to help decision making in family planning. • To psychologically prepare for the onset of disease, or the possibility thereof. • To aid decision making in career choice.

10. How Predictive Testing is Undertaken • A guideline or protocol is used (eg HD protocol). • The condition is verified in an affected relative, and confirmation of genetic test result is obtained. • A patient is seen 1-2 times prior to testing, to discuss the full range of implications and explore feelings wrt potential outcome. • Further appointment for discussion and obtaining blood sample. • Sample if sent to the lab & DNA extracted. • Genetic test is performed and results given in person.

11. Implications of Predictive Testing • Genetic status is confirmed (uncertainty removed). • Risk is clarified in relatives, who can then have testing. • Psychological impact of testing positive – adjustment. • Psychological impact of testing negative: ’survivor guilt’. • Psychological burden of awaiting the onset of disease. • Impact on family dynamics – altered relationships. • Financial – Impact on employment/career opportunities - Impact on insurance cover/discrimination. • Social – Potential for discrimination and stigmatization.

12. Predictive Testing for HD • Can be offered to adults at 50% or 25% risk of developing HD. • Possible contraindications: • mental illness • significant risk of suicide • ongoing pregnancy. • ~30-35% of individuals withdraw after counselling. • 1% risk of ‘catastrophic events’: • Suicide • Attempted suicide • Psychiatric hospitalization.

13. HD Predictive Testing Protocol Referral First Contact (GC) Psychological/ Mental health/ Neurological concerns Continue Withdraw Second Contact Referral to Appropriate Professional Continue Appointment for Testing Continue Appointment for Results Follow up

14. Ethics of Genetic Testing in Children General Principles: • Benefits should outweigh the harm - avoid testing where not so. • Testing should be left until the child is old enough to make his/her autonomous & informed decision. • Genetic testing done only if in child’s best interest. • Those performing testing should be the child’s advocate.

15. Genetic Testing in Children Inappropriate testing: • Testing <12yrs is not justified where there are no clear benefits. • Testing for adult onset disorders (or predictive/ presymptomatic testing) - ie. if child is healthy & no treatment is required.

16. Genetic Testing in Children Predictive/presymptomatic testing:- • Onlyadvocated in diseases which have a childhood onset – eg. FAP. • NOT advocated in those of adult onset – eg. HD.

17. Genetic Testing in Children Appropriate testing: • Disorders of childhood onset • Disorders where early treatment is advocated & available - eg. CF, PKU, haemoglobinopathies. • Disorders where early screening is advocated - eg. FAP.

18. Attitudes to Genetic Testing in Children Parents’ Reasons for wanting their child tested:- • Avoid the worry of uncertainty. • Being able to support children by providing information they are seeking. • Helping prepare for the future. • Avoiding resentment from children in later life. • Encouraging vigilance about preventative screening • Using available technology. • Parents have ‘the right’ to decide.

19. Dilemmas in Childhood Genetic Testing Arise when:- • Parents pressure clinicians to test (inappropriate testing). • Child’s wishes contradict parents’ wishes. • Confidentiality concerns - esp if extended family want child’s information. • Children can give consent if ‘Gillick competent’.

20. Psychosocial Impact of Genetic Testing • Possible long term psychological harm. - Incl. Anxiety, guilt, depression. • Unpredictability of genetic disease. • Possible impact on family relationships. • Removal of child’s autonomy - wrt decision making. • Removal of child’s “right not to know”.

21. Case Study 1: Duchenne MD Family Paul Jane Cheryl Fred Matt

22. Case Study 1: Duchenne Family • 3 year old boy with difficulty climbing stairs. • Referred to Paediatrician by Health Visitor. • S/B Paediatrician who took blood sample for creatinine kinase & DMD analysis. - Note: Parentsunaware of test. • Paediatrician referred child to Paed Neurologist with positive DMD results - (without disclosing results to parents).

23. Case Study 1: Duchenne Family • Parents s/b Paed Neurologist who gave parents these results. • Parents shocked & devastated by unexpected news. • Parents had a second son, aged 6 months when original test performed. • Child subsequently referred to Clinical Genetics once s/b Paed Neurologist. • Parents s/b myself & subsequently by Geneticist.

24. Parents’ Responses to Child’s Diagnosis Outcome: • Parents required a lot of counselling input. -Are continuing to come to terms with diagnoses. • Mother tested positive for DMD carrier status. • Second son tested positive for DMD. • Parents decided against extending their family further. • Are moving to a bungalow and planning adaptions to allow for disabled access.

25. Case Study 2: Ullrich’s MD Family • Pakistani couple referred in for:- 1. Genetic confirmation of their daughters’ diagnosis of Ullrich’s muscular dystrophy. 2. Prenatal diagnosis (PND) for subsequent pregnancy. Note: No testing performed previously in extended family in Pakistan, hence familial mutation unknown and linkage analysis required.

26. Case Study 2: Ullrich’s MD Family Challenges faced in this counselling situation: 1. Language barrier - limited English spoken by father, none by mother [Interpreter used]. 2. Cultural norms – father stated that men: a. ‘tell the women what they need to know’ b. ‘know what is good for their wives & family’ c. ‘make the decisions in society & in the family’. 3. Patient autonomy concerns - father spoke for his wife. 4. Complex genetic diagnosis.