I am an early career clinician researcher. I have a Lecturer position in the Department of Women’s and Children’s Health at UNSW, and am also a practicing Clinical Geneticist, working for the state-wide Genetics of Learning Disability Service. My research passions are how to improve the health outcomes and quality of life for children affected by severe neurodevelopmental disorders, and understand and meet the information and support...view more
I am an early career clinician researcher. I have a Lecturer position in the Department of Women’s and Children’s Health at UNSW, and am also a practicing Clinical Geneticist, working for the state-wide Genetics of Learning Disability Service. My research passions are how to improve the health outcomes and quality of life for children affected by severe neurodevelopmental disorders, and understand and meet the information and support needs of their families.
My clinical research leverages two disruptive approaches: genomics and co-designed new models of care.
My PhD (submitted August 2019) showed how the new genomic diagnostic technologies of exome (ES) and whole genome sequencing (WGS) radically improved diagnosis for a cohort of children with severe early onset epilepsy and neurodevelopmental disability. A diagnosis was established in over 70% of families and this research led directly to the identification and clinical characterisation of 4 novel causes of DEE: variants in PUM1 (Cell), KCNT2 (Cell Reports), ATN1 (American Journal of Human Genetics) and ARV1 (Human Molecular Genetics). The study demonstrated that exome sequencing is cost-effective for the diagnosis of this group of conditions, and that WGS further increases diagnostic yield.
Other published work has delineated several other genomic causes of neurodevelopmental disabilities including two key papers on ZSWIM6 (American Journal of Human Genetics) and CLCN4 (Molecular Psychiatry).
Disappointedly, despite the promise of precision medicine, a genomic diagnosis only directly impacted management in a third of affected individuals with developmental and epileptic encephalopathies. Most children had persistent drug-resistant seizures, and debilitating co-morbidities including moderate-profound intellectual disability, autistic features, additional neurological complications and multi-organ involvement. Mortality rate was 20% over the course of the PhD study. True targeted treatments for other genetic neurodevelopmental disorders are even rarer. Our ongoing UNSW / Sydney Children’s Hospital Network qualitative research study is finding that, despite a genomic diagnosis, many families of children with severe neurodevelopmental disorders report feeling isolated, disempowered and overwhelmed by their children’s complex physical and mental health needs. They report difficulties navigating the health and disability systems, challenges connecting with clinical specialists to receive updates on important information relating to their child and limited access to disease specific information and support resources.
My future research goals are based on two interlinked themes: Theme 1: Narrowing the diagnostic gap for individuals with a suspected neurogenetic conditions. Theme 2: Better leveraging a genetic diagnosis to improve the management and support of individuals with neurogenetics. To meet these goals, I am developing a variety of collaborative translational research strategies. For the first theme, planned strategies include an integrated phenotype and genotype Bioresource to facilitate genomic analysis and natural history studies, collaborations with bioinformaticians and basic scientists to further identify and validate candidate genomic variants, and the development of targeted treatments which can be assessed in clinical trials. Regarding the second theme our clinical research group CoGENES is building research programs with Behavioural Scientists, Health System Researchers and Disability Experts to co-design and evaluate appropriate support and information resources and novel models of care such as a navigator system.
RESEARCH SUPPORT to EP and COGENES group
2019: CoGENES member Suzanne Nevin was successful in a Paediatrio grant for a PhD scholarship.
2018: CoGENES was awarded a Sydney Children's Hospital Foundation Grant for development of information resources for families of children with genetic epilepsy.
In 2017 Dr Palmer was a CI on a successful grant to SPHERE (CAG Chronic Illness in Childhood) which has provided funding for a Project Officer to establish a consented Bioresource for children with epileptic and developmental encephalopathies, conduct qualitative research into the information needs of parents of children with epileptic and developmental encephalopathies, and develop and evaluate resources to support families and physicians including the first SCH Genetic Epilepsy Family Day and genetic information resources for the Paediatric Epilepsy Network NSW https://pennsw.com.au/.
In 2016 Dr Palmer was awarded a NHMRC Postgraduate PhD Scholarship Grant Application and the CoGENES team was awarded a NSW Genomics Collaborative Grant ($180,000) to allow genomic sequencing of 30 trios with undiagnosed developmental and epileptic encephalopathy.
Fellow of the Royal Australasian College of Physicians (Clinical Genetics)(2012)
Diploma in Tropical Medicine and Hygiene, London School of Hygiene and Tropical Medicine, Royal College of Physicians, UK (2006).
Diploma from the royal Australian and New Zealand college of Obstetricians and Gynaecologists (2005).
Membership of the Royal College of Paediatrics and Child Health, UK (2005)
MBBS Royal Free and University College Medical School, London, UK(1999-2002)
University of Oxford, Exeter College, UK (1995-1999)
- 1st BM Pre-clinical Medicine.
- BA HONS in Psychology, Philosophy and Physiology. Class 1.
SCHOLARSHIPS, FELLOWSHIPS AND AWARDS:
UNSW nominee for CSL Florey Next Generation Award (2018)
UNSW Medicine Award for Outstanding Contribution to Research by a Higher Degree Student (2018)
School of Women and Children’s Health, UNSW Junior Conjoint Award (2018)
Senior Presenter prize, UNSW Paediatric Research week (2018)
Diploma in Tropical Medicine and Hygiene (prize for Best Student) and Obstetrics and Child Health (prize for best performance in the oral examination). Twice won the prize for Best Oral Presentation at the Human Genetics Association of Australasia Conference (Clinical Division).
High Distinction in the Unit in Human Genetics (Macquarie University) as part of Fellowship training
Nominee for the Gold Medal for the Universities of London, awarded 8 subject prizes for achievements in examinations and clinical placements and Certificates of Merit (1st, 2nd and 3rd Clinical Years) for overall clinical performance.
Scholar of Exeter College, Oxford University, Fitzgerald Prize and Collection Prizes for academic achievements.
My Research Activities
Clinical Research spotlight: Genetic Epilepsy Collaboration CoGENES
Centre for Clinical Genetics
Clinical Geneticists: Dr Elizabeth Emma Palmer, Dr Rani Sachdev, Professor Edwin Kirk
Genetic Counsellor: Rebecca Macintosh
PhD student: Suzanne Nevin
Department of Neurology
Neurologists: A/Professor Annie Bye (Head of Department), Dr Tejaswi Kandula
Epilepsy Intervention & Evaluation Coordinator: Fleur Le Marne
Epilepsy Clinical Nurse Consultant: Erin Beavis
School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales
Around 200 patients with a likely genetic epilepsy are currently seen by the Departments of Neurology and Clinical Genetics of Sydney Children’s Hospital. This patient cohort presents with diverse epilepsy presentations from severe epileptic encephalopathy, to suspected autosomal dominant genetic generalised epilepsy. Children with severe early onset epilepsy have a particularly high burden of care, requiring frequent inpatient admissions, multiple medications, and with a high risk of comorbidities and premature mortality.
Over 150 patients have undergone extended genetic testing: typically including chromosomal microarray, metabolic screening and next generation sequencing epilepsy panel/exome or genome. Over 70 children have an established genetic diagnosis: with the diagnostic yield varying significantly between patient groups the highest diagnostic yield being in neonatal and early infantile epileptic encephalopathy. Identified genetic causes include variants in: -
- ion channel genes (SCN1A, SCN2A, SCN8A, KCNQ2, KCNT2)
- transporter/synaptic genes (GLUT1, DNM1, SZT2, CNTNAP2, DYNC1H1, WWOX, STXBP1, KIAA2022, UBA5, DEAF1, SLC9A6, SLC6A1, ATP1A3, CDKL5, ARX, PRRT2, WDR73)
- metabolic genes (ARV1, ASNS, ADSL, ALG13, POLG)
Genetic diagnoses are being used by families to guide reproductive decision making and have clinical utility with respect to anti-epileptic medication choice, prognostication, surveillance and management. A team of Clinical Geneticists and Genetic Counsellors navigate families through the testing process and information on diagnoses. Regular clinical/research multidisciplinary meetings are held to guide best clinical practice, and foster ongoing collaborative research.
There is an ideal opportunity to leverage genetic diagnoses to improve clinical care, through a precision medicine approach, and a main goal of CoGenes is to lead collaborative clinical research with immediately translational benefits for patients and their families.
Family and physician support
We develop specific fact-sheets for families on genetic epilepsy conditions, and are developing resources on genetic epilepsy for the PENNSW website https://pennsw.com.au/
We held our inaugrual genetic epilepsy family support day in October 2018, with invited speakers discussing the NDIS, support for families and siblings and advances in genetics and treatments. This family day fostered connections between families, clinicians and researchers so that our clinical research can best meet the needs of families. We work with a variety of family groups including GETA (https://www.geneticepilepsyteam.com.au/)and individual genetic epilepsy support groups.
- Integrating Exome Sequencing into a Diagnostic Pathway for Epileptic Encephalopathy: Evidence of Clinical Utility and Cost Effectiveness. Collaborators: Professor Deborah Schofield, Macquarie University, SEALS Genetic Laboratory and The Garvan Institute. This study supports the integration of exome sequencing and gene panel testing into the diagnostic pathway for epileptic encephalopathy, both in terms of cost-effectiveness and clinical utility. Trio exome sequencing resulted in a diagnostic yield of 50% with a cost saving of AU$5,236 per additional diagnosis compared to standard testing. (Palmer, Schofield et al., 2018). Funding: NHMRC.
- The Information Needs Of Parents Of Children With A Genetic, Or Suspected Genetic, Form Of Epilepsy. Collaborator Professor Claire Wakefield, UNSW. Funding: SPHERE, Pediatrio, Sydney Children's Hospital Foundation. This qualitative study involves in depth interviews of parents with a child with suspected or confirmed genetic epilepsy being conducted by Ms Suzanne Nevin, will inform the provision of information for families and doctors of children with a genetic epilepsy, through the established Epilepsy Resource for families http://www.pennsw.com.au/
- Identification and characterisation of novel genetic causes of developmental and epileptic encephalopathy (DEE) by Whole Genome Sequencing (WGS). 30 families are currently being investigated by whole genome sequencing in collaboration with the Translational Genomics Group at the Garvan Institute. Mechanisms including somatic mosaicism, mitochondrial and complex structural rearrangements are being evaluated. A diagnosis of over 70% has been achieved to date. This research is leading to the identification of novel genetic causes of EE. Our group has identified 4 novel causes of DEE in PUM1 (Cell), KCNT2 (Cell Reports), ATN1 (American Journal of Human Genetics) and ARV1 (Human Molecular Genetics). With several more new genetic disorders / genetic mechanisms being evaluated with international collaborations. Funding: OHMR and NHMRC.
- A Precision Medicine Approach to Genetic Epilepsy: the Genetic Epilepsy BioResource. In collaboration with the Sydney Partnership for Health, Education, Research & Enterprise (SPHERE) we are developing a comprehensive, consented patient and family database, including biobanking of patient derived samples and detailed phenotypic and genotypic data storage. This BioResource will facilitate further clinical collaborative research and evidence-based clinical management. Overall aims include evaluation of underlying pathophysiology and natural history of genetic epilepsy conditions and exploration of avenues for personalised management to maximise clinical outcomes for our patients, including enrolment in relevant clinical trials.
- EP with Dr Deepak Gill from CHW, are NSW Co-leads for the Australian Genomics Health Alliance Epileptic Encephalopathy Flagship, led by Professor Ingrid Scheffer.
- EP is a board member of the K2A SPHERE CAG
- CoGenes has strong links with world class Australian and international neuroscience, pharmacology and genomics researchers (see selected publications below).
- Members of the CoGenes team are moderators of the Human Disease Gene Webseries (e.g. EP for SCN2A, ATN1, IQSEC2, CLCN4, ZSWIM6, IQSEC2, PUM1 and THOC2). http://humandiseasegenes.nl/
Selected recent publications
- Gennarino VA;Palmer EE;McDonell LM;Wang L;Adamski CJ;Koire A;See L;Chen CA;Schaaf CP;Rosenfeld JA;Panzer JA;Moog U;Hao S;Bye A;Kirk EP;Stankiewicz P;Breman AM;McBride A;Kandula T;Dubbs HA;Macintosh R;Cardamone M;Zhu Y;Ying K;Dias KR;Cho MT;Henderson LB;Baskin B;Morris P;Tao J;Cowley MJ;Dinger ME;Roscioli T;Caluseriu O;Suchowersky O;Sachdev RK;Lichtarge O;Tang J;Boycott KM;Holder JL;Zoghbi HY, 2018, 'A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures', Cell, vol. 172, pp. 924 - 932.e11, http://dx.doi.org/10.1016/j.cell.2018.02.006
- Palmer EE;Hong S;Al Zahrani F;Hashem MO;Aleisa FA;Ahmed HM J;Kandula T;Macintosh R;Minoche AE;Puttick C;Gayevskiy V;Drew AP;Cowley MJ;Dinger M;Rosenfeld JA;Xiao R;Cho MT;Yakubu SF;Henderson LB;Guillen Sacoto MJ;Begtrup A;Hamad M;Shinawi M;Andrews MV;Jones MC;Lindstrom K;Bristol RE;Kayani S;Snyder M;Villanueva MM;Schteinschnaider A;Faivre L;Thauvin C;Vitobello A;Roscioli T;Kirk EP;Bye A;Merzaban J;Jaremko Ł;Jaremko M;Sachdev RK;Alkuraya FS;Arold ST, 2019, 'De Novo Variants Disrupting the HX Repeat Motif of ATN1 Cause a Recognizable Non-Progressive Neurocognitive Syndrome', American Journal of Human Genetics, vol. 104, pp. 542 - 552, http://dx.doi.org/10.1016/j.ajhg.2019.01.013
- Lanoue V; Chai YJ; Brouillet J; Weckhuysen S; Palmer EE; Frederic A Meunier, 2019, ‘STXBP1-encephalopathy: connecting neurodevelopmental disorders with alpha-synucleinopathies?’ Neurology, vol.93(3), pp. 114-123. http://dx.doi.org/10.1212/WNL.0000000000007786
- Nabais Sá MJ;Jensik PJ;McGee SR;Parker MJ;Lahiri N;McNeil EP;Kroes HY;Hagerman RJ;Harrison RE;Montgomery T;Splitt M;Palmer EE;Sachdev RK;Mefford HC;Scott AA;Martinez-Agosto JA;Lorenz R;Orenstein N;Berg JN;Amiel J;Heron D;Keren B;Cobben JM;Menke LA;Marco EJ;Graham JM;Pierson TM;Karimiani EG;Maroofian R;Manzini MC;Cauley ES;Colombo R;Odent S;Dubourg C;Phornphutkul C;de Brouwer AP M;de Vries BB A;Vulto-vanSilfhout AT, 2019, 'De novo and biallelic DEAF1 variants cause a phenotypic spectrum', Genetics in Medicine, http://dx.doi.org/10.1038/s41436-019-0473-6
- Palmer EE;Schofield D;Shrestha R;Kandula T;Macintosh R;Lawson JA;Andrews I;Sampaio H;Johnson AM;Farrar MA;Cardamone M;Mowat D;Elakis G;Lo W;Zhu Y;Ying K;Morris P;Tao J;Dias KR;Buckley M;Dinger ME;Cowley MJ;Roscioli T;Kirk EP;Bye A;Sachdev RK, 2018, 'Integrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: Evidence of clinical utility and cost effectiveness', Molecular Genetics and Genomic Medicine, vol. 6, pp. 186 - 199, http://dx.doi.org/10.1002/mgg3.355
- Palmer EE;Stuhlmann T;Weinert S;Haan E;Van Esch H;Holvoet M;Boyle J;Leffler M;Raynaud M;Moraine C;Van Bokhoven H;Kleefstra T;Kahrizi K;Najmabadi H;Ropers HH;Delgado MR;Sirsi D;Golla S;Sommer A;Pietryga MP;Chung WK;Wynn J;Rohena L;Bernardo E;Hamlin D;Faux BM;Grange DK;Manwaring L;Tolmie J;Joss S;Study DD D;Cobben JM;Duijkers FA M;Goehringer JM;Challman TD;Hennig F;Fischer U;Grimme A;Suckow V;Musante L;Nicholl J;Shaw M;Lodh SP;Niu Z;Rosenfeld JA;Stankiewicz P;Jentsch TJ;Gecz J;Field M;Kalscheuer VM, 2018, 'De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females', Molecular Psychiatry, vol. 23, pp. 222 - 230, http://dx.doi.org/10.1038/mp.2016.135
- Palmer EE*;Kumar R*;Gordon CT*;Shaw M;Hubert L;Carroll R;Rio M;Murray L;Leffler M;Dudding-Byth T;Oufadem M;Lalani SR;Lewis AM;Xia F;Tam A;Webster R;Brammah S;Filippini F;Pollard J;Spies J;Minoche AE;Cowley MJ;Risen S;Powell-Hamilton NN;Tusi JE;Immken LD;Nagakura H;Bole-Feysot C;Nitschké P;Garrigue A;de Saint Basile G;Kivuva E;Scott RH;Rendon A;Munnich A;Newman W;Kerr B;Besmond C;Rosenfeld JA;Amiel J;Field M;Gecz J, 2017, 'A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations', American Journal of Human Genetics, vol. 101, pp. 995 - 1005, http://dx.doi.org/10.1016/j.ajhg.2017.10.009
- Gururaj S*;Palmer EE*;Sheehan GD;Kandula T;Macintosh R;Ying K;Morris P;Tao J;Dias KR;Zhu Y;Dinger ME;Cowley MJ;Kirk EP;Roscioli T;Sachdev R;Duffey ME;Bye A;Bhattacharjee A, 2017, 'A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion Selectivity and Causes Epileptic Encephalopathy', Cell Reports, vol. 21, pp. 926 - 933, http://dx.doi.org/10.1016/j.celrep.2017.09.088
- Von Spiczak S;Helbig KL;Shinde DN;Huether R;Pendziwiat M;Lourenço C;Nunes ME;Sarco DP;Kaplan RA;Dlugos DJ;Kirsch H;Slavotinek A;Cilio MR;Cervenka MC;Cohen JS;McClellan R;Fatemi A;Yuen A;Sagawa Y;Littlejohn R;McLean SD;Hernandez-Hernandez L;Maher B;Møller RS;Palmer E;Lawson JA;Campbell CA;Joshi CN;Kolbe DL;Hollingsworth G;Neubauer BA;Muhle H;Stephani U;Scheffer IE;Pena SD J;Sisodiya SM;Helbig I, 2017, 'DNM1 encephalopathy', Neurology, vol. 89, pp. 385 - 394, http://dx.doi.org/10.1212/WNL.0000000000004152
- Palmer EE*;Jarrett KE*;Sachdev RK;Zahrani FA;Hashem MO;Ibrahim N;Sampaio H;Kandula T;Macintosh R;Gupta R;Conlon DM;Billheimer JT;Rader DJ;Funato K;Walkey CJ;Lee CS;Loo C;Brammah S;Elakis G;Zhu Y;Buckley M;Kirk EP;Bye A;Alkuraya FS;Roscioli T;Lagor WR, 2016, 'Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy', Human Molecular Genetics, vol. 25, pp. 3042 - 3054, http://dx.doi.org/10.1093/hmg/ddw157
- Zerem A;Haginoya K;Lev D;Blumkin L;Kivity S;Linder I;Shoubridge C;Palmer EE;Field M;Boyle J;Chitayat D;Gaillard WD;Kossoff EH;Willems M;Geneviève D;Tran-Mau-Them F;Epstein O;Heyman E;Dugan S;Masurel-Paulet A;Piton A;Kleefstra T;Pfundt R;Sato R;Tzschach A;Matsumoto N;Saitsu H;Leshinsky-Silver E;Lerman-Sagie T, 2016, 'The molecular and phenotypic spectrum of IQSEC2-related epilepsy', Epilepsia, vol. 57, pp. 1858 - 1869, http://dx.doi.org/10.1111/epi.13560
- Smogavec M;Cleall A;Hoyer J;Lederer D;Nassogne MC;Palmer EE;Deprez M;Benoit V;Maystadt I;Noakes C;Leal A;Shaw M;Gecz J;Raymond L;Reis A;Shears D;Brockmann K;Zweier C, 2016, 'Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and phenotypic spectrum', Journal of Medical Genetics, vol. 53, pp. 820 - 827, http://dx.doi.org/10.1136/jmedgenet-2016-103880
- Palmer EE*;Hayner J*;Sachdev R;Cardamone M;Kandula T;Morris P;Dias KR;Tao J;Miller D;Zhu Y;Macintosh R;Dinger ME;Cowley MJ;Buckley MF;Roscioli T;Bye A;Kilberg MS;Kirk EP, 2015, 'Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine', Molecular Genetics and Metabolism, vol. 116, pp. 178 - 186, http://dx.doi.org/10.1016/j.ymgme.2015.08.007
NHMRC, SPHERE: Sydney Partnership for Health, Education, Research & Enterprise, NSW Health including the NSW Genomics Collaborative Grants Program, The Kinghorn Foundation, Pediatrio, Sydney Children's Hospital Foundation
My Research Supervision
Areas of supervision
Genomics, Clinical Genetics, Intellectual disability, autism, epilepsy and other neurodevelopmental disorders, psychosocial support for families and genetic counselling, disability and co-design.
Keen to discuss with potential ILP, Masters and PhD candidates.
Dr Palmer has supervised two Masters of Genetic Counselling (University of Sydney) students who successfully graduated in 2018 and 2019. I am currently supervising a Masters student and on the supervisory panel for a PhD student.
Qualitative study: The Information Needs Of Parents Of Children With A Genetic, Or Suspected Genetic, Form Of Epilepsy (HREC/SCHN). Collaborator Professor Claire Wakefield, UNSW. This qualitative study is asking parents of children with genetic epilepsy about their information and support needs to inform the development of multimedia information resources for families and doctors of children with a genetic epilepsy, through the PENNSW website. http://www.pennsw.com.au/
Coordinator: Inaugural NSW Sydney Children’s Hospital Genetic Epilepsy Family Day (October 2018).
Speaker: GETA Conference 2019. To see the conference https://www.geneticepilepsyteam.com.au/conference-2019/speakers/palmer/
The CoGenes group is establishing a Community Reference Board for our research.
Moderator for 7 genetic causes of ID/ASD on the Human Disease Gene and GenIDA Websites http://humandiseasegenes.nl https://genida.unistra.fr/ (SCN2A, ZSWIM6, THOC2, ATN1, IQSEC2, PUM1, PCHDH1.
I am a lecturer for UNSW Medicine students (Phase 1 and in 2020 Phase 3 students), the University of Sydney GMED5001 Genomics in Clinical Practice course, and recently on the Masters of Genetic Counselling and Genomics in Medicine courses (University of Sydney). I frequently lecture on genetics and new genomic techniques, including for the Royal Australian College of Paediatrics Clinical Genetics Fellowship trainees.