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The Experience of the first adult
Neurogenetics Clinic in Ireland
Dr Diana Olszewska (Neurology), Dr Terri McVeigh (Genetics), Professor Tim Lynch (Neurology)
Heritable Neurological Disease
• A number of neurological conditions have a genetic aetiology – Implications for wider family– Incurable disease
• Most can be handled appropriately within a routine neurology clinic with onward referral for genetic counselling if necessary
• e.g. Huntington’s disease
• However, some specific cases are complex, rare or uncertain and benefit from multi-disciplinary input
• It is recommended that there be a minimum of 1 clinical genetics post and 1 neurology post designated for Neurogenetics service for a population of 2 million1
1. Genetic Services for Neurological Disorders, ABN and Clinical Genetics Society Report, 2003
Neurology
• Rare disorders require extensive literature review and specialist diagnostic approach• Time constraints in routine clinics does not
facilitate this easily
• Limited time for explanation of inheritance, recurrence risks• Patient concerns regarding family planning,
prenatal diagnosis
• Practical issues regarding send-out of samples to specialist laboratories
Genetics
• Complex genetic conditions require careful explanation regarding natural history and implications for prognosis, family planning, and recurrence risk
• Genetic testing can be directed based on careful phenotyping
• Waiting list – Priority <4 months
– Routine ..6-18 months!
• Frequent failure to attend
• Hesitance in proceeding with pre-symptomatic testing
https://www.eshg.org/111.0.html.
Teamwork!
• Can combined clinic address these issues?
• Neurogenetics clinic
– 1 neurologist + 1 geneticist
• Real-time phenotyping
• Active discussion regarding possible differential diagnoses
• Valuable opportunity for detecting important or unresolved genetic issues
• Foundation for genetic counselling
Patient simultaneously reviewed by Registrars
1 Neurology
1 Genetics
Simultaneous review by Consultants
1 Neurology
1 Genetics
Brainstorming!
Likely diagnosis suggested
Workflow
• Detailed history • Personal and familial
• Pedigree drawing • Thorough neurological examination • Review of investigations performed to date
• Review of case
• Active patient input in discussion• Literature review • Differential diagnosis
• Specialist tests requested
• Inheritance pattern and recurrence risks outlined
Benefits
• Two heads are better than one! – Widens differential diagnosis
• One clinic visit – Reduced repetition for patient– Time efficient – Family members can attend together or separately
• Familiarity with Dublin Neurological Institute – Less anxiety
• Improves doctor-patient relationship• Active participation in discussion • Patient understands the process better• Dedicated “team” of doctors working on rare disorder
A bridge to Crumlin
• Introduction of concept of genetic counselling and/or pre-symptomatic testing for unaffected family members
– Can explain process
– Allay anxiety surrounding “the test”
• Explain no obligation
• Define risk to patient and family members
– Continuity of care
• Genetic registrar working in Department of clinical genetics
The Adult Neurogenetic ClinicDublin Neurological Institute
• First and only one in Ireland
• Once a month
• Commenced November 2014
• 1.5h dedicated per patient
– Reviewed by 4 doctors
Neurogenetic clinic
• 25 patients
– 16 families
– 3 returns
• Age 22-78
All-Ireland Service
Disorder N Action
Frontotemporal Dementia 10 Referral for Genetic Counselling /Pre-symptomatic testing Different genes in different families: MAPT, GRNAdvice re prenatal pre-implantation diagnosis Referral for psychology input 1 patient: Review of diagnosis - personality later attributed to organic (reversible) cause!
Leucodystrophy 1 Referral to international specialist
Ataxia-Telangiectasia 1 Referral for genetic counselling Advice for cancer risk for heterozygous carriers in family
Parkinson’s disease 3 Young onset – Parkin testing (n=2, 1 positive, 1 negative)Older onset (familial) – LRRK2 testing
Pure ataxia 2 Extensive diagnostic work up
Spastic Ataxia 2 Further testing (unknown genetic aetiology after multiple tests)
GLUT 1 deficiency 1 Referral for genetic counsellingConsideration: Triheptanoin therapy
Spinocerebellar ataxia with writer’s cramp
1 Diagnosis – SCA6
Familial MS 1 Counselling regarding potential genetic contribution Discussion re limitations of available genetic investigations
• Multiple family members affected• New mutation “+15”, dominant inheritance
– 50-50 chance
• Numerous members of the family: – 4 siblings – 1 cousin – 1 son
• Referral to Crumlin for counselling and pre-symptomatic testing
Brain. 2015 Oct;138(Pt 10):3100-9. By Prof T Lynch
Glut 1 deficiency
• 22 year old female • Episodic Myoclonic dystonia and tremor
– Increasing frequency with stress, fatigue, heat– Significant impact on quality of life
• No family history of note • Test:
– Next generation panel: Dystonia and Parkinsonism – Mutation identified in SLC2A1
• ? De novo event (father is deceased, mother unaffected)• 50/50 recurrence risk
• Declined referral for genetic counselling– Felt she had enough information for now
By Dr T McVeigh
Summary of outcomes
• Twenty-five patients have attended a pilot clinic
• Identification of pathogenic mutations directed screening and treatment, and facilitated onward referral of family members for genetic counselling (n=8, 33%).
• A number of novel mutations were identified in MAPT (“missing tau” mutation), SLCA1 and Progranulin.
• A number of patients had phenotypic features not previously reported; e.g. writer’s cramp in SCA6; paroxysmal myoclonus in GLUT1 deficiency.
Summary of outcomes II
• Appropriate referrals were made for non-neurological sequelae of genetic mutations, e.g. breast cancer screening for carriers of ATM mutations.
• New treatments were considered based on genetic diagnoses, e.g. triheptanoin in GLUT1 deficiency.
• We appropriately referred undiagnosed complex patients (n=2) to international experts.
Conclusions
• The Neurogenetics clinic
– Addresses a gap in service provision for complex families with neurogenetic disorders
– Allows timely identification of rare and atypical diagnoses.
• Role for other disciplines
– Psychology
– Cardiology for muscular dystrophies?
Neurogenetics
• Rare single gene disorders account for a small proportion of neurological presentations
– But require specific awareness, recognition and specialist referral
• Thank you