BIALLELLIC CUBN VARIANTS AS A CAUSE OF ISOLATED PROTEINURIA- CHALLENGING THE INVESTIGATIVE PARADIGM

K JAYASINGHE1,2,3, C QUINLAN2,4,5, C SIMONS2,7, S WHITE2,6, A MALLETT4,8
1Department of Nephrology, Monash Health, Melbourne, Australia, 2Murdoch Childrens Research Institute (MCRI), Melbourne, Australia, 3Monash University, Melbourne, Australia, 4KidGen Renal Genetics Flagship, Australian Genomic Health Alliance, Australia, 5Department of Paediatric Nephrology, Royal Children’s Hospital, Melbourne, Australia, 6Department fo Paediatrics, Royal Children’s Hospital, Melbourne, Australia, 7University of Queensland, Brisbane, Australia, 8Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia

Background: Proteinuria is a common kidney presentation. Historically, diagnostic workup of patients with isolated proteinuria involved thorough urinalysis, imaging and blood sampling before potentially proceeding to renal biopsy. However recent advances have resulted in reduced cost and increased availability of genomic sequencing for establishing clinical diagnoses.
Case Report: An 8 year old boy was referred with an incidental finding of persistent proteinuria during investigation for nonspecific abdominal pain. He had no haematuria and had normal serum albumin. All other investigations including blood analysis for haematological, biochemical and immunology parameters, renal ultrasound, ophthalmology and audiology assessment were unremarkable. Further assessment revealed consanguineous family history and a brother also with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global uniform thinning of the glomerular basement membrane on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~4.5% of the genome. Shared regions of LCSH between the brothers were identified using the Genomic Oligoarray and single nucleotide polymorphism (SNP) Evaluation tool. Examination of these regions implicated CUBN, on chromosome 10p12.31. Research whole genome sequencing of both affected individuals was performed after informed consent (HREC/15/QRCH/126). This revealed a homozygous stop-gained variant in CUBN (NM_001081.3, c.4689_4690delTAinsAT, p.(CysIle1263*), ACMG Class 5).
Conclusions: CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia. Therefore, we describe how genomics can successfully identify single gene causes of nephropathy. This presents a case for genomic sequencing to be undertaken earlier in the diagnostic workup to reduce the need for invasive investigations, challenging the current diagnostic paradigm.


Biography:
Dr Cathy Quinlan is a Paediatric Nephrologist in The Royal Children’s Hospital and Honorary Research Fellow at the Murdoch Childrens Research Institute. A graduate of University College Dublin, she completed her clinical training in the Children’s University Hospital in Dublin and Great Ormond Street Hospital in London. She completed research towards an MSc in Medical Education in Queens University Belfast and MD(Res) in University College London investigating the cardiovascular phenotype in juvenile-onset lupus before moving to the Melbourne Children’s Campus in 2013. Her research interests include inherited kidney disease, nephrotic syndrome, cystic fibrosis renal disease and peritoneal dialysis

PATIENT AND CAREGIVER BELIEFS, ATTITUDES AND PERSPECTIVES ON GENETIC SCREENING AND TESTING FOR AUTOSOMAL POLYCYSTIC KIDNEY DISEASE

C LOGEMAN1,2, Y CHO3,4,5, B SAUTENET6, G RANGAN7, T GUTMAN1,2, J CRAIG1,2, A ONG8, A CHAPMAN9, C AHN10, H COOLICAN11, J TZE-WAH KAO12,13, R GANSEVOORT14, R PERRONE15, T HARRIS16, V TORRES17, Y PEI18, P KERR19, J RYAN19,  A VIECELLI3, C GENESTE6, Y KIM10, M HOWELL1,2, A JU1,2, K MANERA1,2, A TEIXEIRA-PINTO1,2, A TONG1,2
1Centre For Kidney Research, Westmead, Australia, 2School of Public Health, The University of Sydney, Sydney, Australia, 3Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia, 4Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia, 5Translational Research Institute, Brisbane, Australia, 6Department of Nephrology and Clinical Immunology, Tours Hospital, University Francois Rabelais, Tours, France, 7Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, Australia, 8Academic Nephrology Unit, Department of Infection Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom, 9Department of Medicine, The University of Chicago, Chicago, United States, 10Division of Nephrology, Seoul National University Hospital, , Seoul, South Korea, 11Polycystic Kidney Disease Foundation of Australia, , Australia, 12School of Medicine, Fu Jen Catholic University, , Taiwan, 13Department of Internal Medicine, National Taiwan University Hospital, , Taiwan, 14Faculty of Medical Sciences, University Medical Center Gronigen, , Netherlands, 15Division of Nephrology, Tufts University School of Medicine, , United States, 16Polycystic Kidney Disease International, , United Kingdom, 17Department of Nephrology and Hypertension, Mayo Clinic, , United States, 18Division of Nephrology and Division of Genomic Medicine, University of Toronto, , Canada, 19Department of Nephrology, Monash Medical Centre and Monash University, Melbourne, Australia

Aim: To describe patient and caregiver perspectives on the value and risks of genetic screening and testing for autosomal polycystic kidney disease (ADPKD).
Background: Predictive genetic screening and testing is available for accurate and early diagnosis of hereditary autosomal polycystic kidney disease. However, the complex ethical and psychosocial implications can make decision-making challenging and data on patients’ perspectives are limited.
Methods: 154 participants (120 patients and 34 caregivers) from 8 centres in Australia, France and Korea participated in 17 focus groups. Transcripts were analysed thematically.
Results: We identified five themes: financial constraints (insecurity in the inability to obtain life insurance, self-doubt in limited work opportunities, financial barrier of test); futility in unpredictability (accepting erratic and diverse manifestation of disease, inevitable disease progression, daunted by perplexity of results); lacking autonomy and support in decisions (overwhelmed by ambiguous information, medicalising family planning, appeasing the family, financial barrier); seizing control of wellbeing (gaining confidence through disease management, reassurance in family resilience, hope for health innovations to benefit the next generation, minimalising regret with preparation); and anticipating impact on quality of life (comforted by lack of symptoms, decisional uncertainty in risk of inheriting PKD, judging the value of life with PKD in family planning, guilt in foetal testing or abortion).
Conclusions: For patients with ADPKD, genetic screening or testing provides an opportunity for them to take ownership of their health through family planning and preventive measures. However, they are also concerned and uncertain about the accessibility of these services, psychological sequelae of testing, and potential financial consequences. Patient-centred genetic counselling and education that addresses patients’ concerns may support informed decision-making about genetic testing and screening in ADPKD.


Biography:
Miss Logeman is a research officer at the Centre for Kidney Research . She undertook her Honours Bachelor of Science in Canada from the University of Guelph focusing on molecular biology and genetics. She graduated with a Masters of Public Health from the University of Sydney in 2017. She is currently on the coordinating committee for the Standardised Outcomes in Nephrology (SONG) initiative and the Patient-Centred Research Network (PACER).

RENAL ANGIOMYOLIPOMAS IN TUBEROUS SCLEROSIS COMPLEX: A CASE REPORT AND LITERATURE REVIEW

P WU1, A WANG2,3
1Royal North Shore Hospital, Sydney,, Australia, 2The George Institute for Global Health, Sydney,, Australia, 3Faculty of Medicine and Health Sciences, Macquarie University, Sydney,, Australia

Background: Renal angiomyolipomas are a common feature of tuberous sclerosis complex (TSC), occurring in up to 80% of cases. Large renal angiomyolipomas are at high risk of spontaneous rupture and are associated with significant morbidity and mortality
Case Report: We report a case of a 21-year-old Chinese male who was initially diagnosed with polycystic kidney disease (PKD) in China with findings of multiple bilateral renal lesions and a significant family history of PKD on the paternal side. His past medical history includes febrile convulsions and epilepsy. He presented with intermittent bilateral flank pain. Repeat abdominal CT scans demonstrated innumerable bilateral angiomyolipomas with the largest measuring 8cm in diameter in the right lower pole which had significantly increased in size from previous imaging. In view of his symptomatic angiomyolipoma, he subsequently underwent a successful CT-guided selective embolization of this right-sided lesion. He then developed recurrent epilepsy. A brain MRI demonstrated right occipital tubers. Although chromosome microarray testing of 16p13.3 and TSC 1/2 gene returned normal results, based on the guidelines of having two major features of seizures with consistent changes on MRI brain and multiple (>2) angiomyolipomas, he was clinically diagnosed with TSC. His surveillance abdominal imaging 12 months following embolization showed the largest angiomyolipoma was reduced to 4cm. A trial of pharmacological treatment with mTOR-inhibitors would be considered if his angiomyolipoma enlarges again.
Conclusion: Approximately 10-25% of TSC patients have no mutations in TSC1/2 gene, which does not exclude the diagnosis. Continued surveillance of renal angiomyolipomas with abdominal imaging every 1–3 years is recommended to monitor disease stability. Management of renal angiomyolipomas in TSC includes use of mTOR-inhibitors or surgical intervention of selective embolization.


Biography:
I am a PGY2 doctor in training with aspirations to pursue physician training and specialise in an Oncology career.
I have a particular interest in genetics and molecular biology of genitourinary and gastrointestinal malignancies.

IMPLEMENTING GENOMICS INTO NEPHROLOGY SERVICES- A REVIEW OF THE LITERATURE AND STUDY PROTOCOL

K JAYASINGHE1,2,3, Z STARK2,6, AJ MALLETT3,8, C QUINLAN2,3,5, S BEST4
1Monash Health, Melbourne, Australia, 2Murdoch Childrens Research Institute (MCRI), Melbourne, Australia, 3KidGen Renal Genetics Flagship, Australian Genomics Health Alliance, Australia, 4Macquarie University, Sydney, Australia, 5Department of Paediatric Nephrology, Royal Children’s Hospital, Melbourne, Australia, 6Department fo Paediatrics, Royal Children’s Hospital, Melbourne, Australia, 7University of Queensland, Brisbane, Australia, 8Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia

Introduction: Genomics has rapidly advanced understanding of many inherited kidney disorders. However, there is a discrepancy with clinicians’ use of genomics in routine clinical care. This study has two aims: review the literature to identify barriers that may hinder implementation of genomics in adult nephrology; and to set out a theory-informed research plan on adult nephrologist uptake of clinical genomics.
Literature Review: We searched PubMed and MEDLINE for original and review articles until 28/02/2018 on nephrologists’ knowledge and practice of genomics/genetics. Given the paucity of data, we also included other subspecialists. Most studies focused on oncologists, obstetricians/gynecologists and general physicians. Many lacked a theoretical basis. Emerging themes were needs for effective education strategies and organizational support, and importance of genetic counsellors facilitating implementation.
Study Protocol: The literature review informed the study protocol. Specifically, a web-based cross-sectional survey was developed to evaluate barriers and facilitators to the uptake of genomics amongst Australian nephrologists and trainees. The Consolidated Framework for Implementation Research (CFIR) is a well-utilized, multi-level implementation theory-informed framework applicable in study designs. Questions were based around the CFIR, validated by an expert team in implementation and survey design and further revised following feedback from a pilot survey. Participants were queried regarding their perception/attitude towards genetic testing, preferred method of learning about genetics/genomics, and preferences in terms of support and model of service delivery to establish a baseline of practitioner views to guide further research and implementation strategies.
Conclusion: There is a lack of literature reporting nephrologists’ knowledge and practice of genomics/genetics, though themes from other subspecialties are informative. A CFIR-based survey to clarify this has been generated and piloted and will be deployed between 8-12/09/2018.


Biography:
Dr. Jayasinghe  graduated from medical school at Monash University in 2010. She undertook her basic physician training at Monash Health, followed by nephrology advanced training in nephrology at the Royal Prince Alfred Hospital, Concord Hospital in Sydney and Monash Health in Melbourne. She completed a Master of Medicine (Clinical Epidemiology) in 2017. Dr Jayasinghe was awarded her Fellowship of the Royal Australian College of Physicians in Nephrology in 2017. Her PhD programme within Monash Clinical School will investigate the clinical utility and cost effectiveness of whole exome sequencing in patients with inherited kidney disease.

AUSTRALIAN RENAL GENE PANELS (ARGP): RESULTS FROM FOUR YEARS OF TESTING

HJ MCCARTHY1,2,3, AJ MALLETT3,4, G HO3,5, K HOLMAN3,5,  E FARNSWORTH3,5, C PATEL3,6, JT FLETCHER3,7,  A MALLAWAARACHCHI3,8, C QUINLAN3,9, B BENNETTS2,3,5, SI ALEXANDER1,2,3
1Department of Nephrology, Children’s Hospital at Westmead, Westmead, Australia, 2University of Sydney, Sydney, Australia, 3KIDGEN Collaborative Rare Disease Flagship, Melbourne, Australia, 4Kidney Health Service and Conjoint Renal Research Laboratory, Royal Brisbane & Women’s Hospital and CKD.QLD and School of Medicine, University of Queensland, Brisbane, Brisbane, Australia, 5Sydney Genome Diagnostics, Westmead, Australia, 6Genetic Health Queensland, Royal Brisbane & Women’s Hospital, Brisbane, Australia, 7Department of Paediatrics, Centenary Hospital for Women and Children, Canberra, Australia , 8Department of Clinical Genetics, Royal Prince Alfred Hospital, Sydney, Australia, 9Royal Children’s Hospital , Melbourne, Australia

Aim: Review of test results from four years of renal gene panel testing.
Background: Genomic assessment is becoming a routine component of diagnostic work up for both paediatric and adult renal patients. Renal Genetic Clinics are established in almost all states and territories and access to sequencing is integral to their functionality. The ARGP service from Children’s Hospital at Westmead provides a regional NATA accredited diagnostic sequencing service for 22 renal gene panels.
Methods: A multidisciplinary team of nephrologists, clinical and molecular geneticists was established to curate the panels, review referrals/reports and provide advice if required to referring clinicians. Targeted exome panels utilise an Illumina TruSight One panel capture, sequencing using Illumina HiSeq 2500 or NextSeq 550 and variant classification is according to the ACMG guidelines. Gaps in genes of interest are backfilled as required using Sanger sequencing.
Results: 436 referrals for 414 families have been received from all New Zealand and all Australian states/territories (55% female and 51% paediatric at time of referral). In 39% of 315 reported results a disease causing variant (DCV) was found (13% variant of uncertain significance, 48% negative). Variants of interest were identified in 72 of the 225 genes represented, COL4A5 was reported 32 times. Detection rates did not differ significantly between adult and paediatric referrals except in Tubular/Metabolic renal panels (50% adults and 75% paediatric had a DCV); and AD tubulointerstitial disease (25% adults and 0% paediatric had a DCV).
Discussion: This regional service provides an expanded role in clinical advice/sequencing for health professionals investigating genetic aetiology of renal disease with increasing panels available. Future move to whole exome capture will further improve the diagnostic hit rate.


Biography:
Dr Hugh McCarthy trained as a paediatric nephrologist in the UK where he completed his PhD in the genetics of steroid resistant nephrotic syndrome. This also involved establishing a national rare renal disease registry (RADAR); he is developing an Australasian equivalent registry (ARRK). Other than rare disease patient registries, his research interests include renal genomics and the pathogenesis of non genetic nephrotic syndrome.

ADULT-DIAGNOSED NON-SYNDROMIC NEPHRONOPHTHISIS IN AUSTRALIAN FAMILIES CAUSED BY BIALLELIC NPHP4 VARIANTS

R HUDSON1, C PATEL2,  C HAWLEY3,  S O’SHEA4, P SNELLING5, J CRAWFORD6,  C SIMONS7, AJ MALLETT8
1Department of Renal Medicine, Royal Brisbane And Womens Hospital, Herston, Australia, 2Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Herston, Australia , 3Department of Nephrology, Princess Alexandra Hospital, Wooloongabba, Australia, 4Wesley Hospital,  Auchenflower, Australia, 5Department of Nephrology, Royal Prince Alfred Hospital, Camperdown, Australia, 6Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia, 7Murdoch Children’s Research Institute, Parkville, Australia, 8Faculty of Medicine, The University of Queensland, Herston,

Aim: To identify the genetic cause of adult-diagnosed non-syndromic nephronophthisis in two Australian families with genetically unresolved inherited kidney disease.
Background: There is increasing appreciation of nephronophthisis as an autosomal recessive cause of chronic and end-stage kidney disease (ESKD/CKD) amongst adults. Whilst NPHP1 has long been recognised as causative for this disorder, we propose NPHP4 as an additional genetic aetiology for such presentations.
Methods: Two families with presumed adult-diagnosed non-syndromic nephronophthisis and negative diagnostic genetic testing were identified from the RBWH Conjoint Renal Genetics Clinic. Both included two affected siblings and there was no extra-renal phenotype. After informed consent (HREC/14/QRBW/34) research whole genome sequencing was undertaken with custom in-house bioinformatic analysis.
Results: Biallelic NPHP4 variants were identified in trans and clinically confirmed in all four affected individuals from both families confirming a genetic diagnosis.In family 1, participant 1 (F1P1) was diagnosed at 19years with ESKD. Their affected younger sibling (F1P2) reached ESKD at 15years after renal biopsy at 14years suggested nephronophthisis. The variants detected were NPHP4 (NM_015102.4)c.3766C>T;p.(Gln1246*) and 1p36.31del; both ACMG Class5. The heterozygous 1p36.31(5955751_5979349) deletion was previously not detected with diagnostic sequencing.In family 2, participant 3 (F2P3) reached ESKD at 27years having undergone renal biopsy at 26years suggesting nephronophthisis. Their affected younger sibling (F2P4) had CKD Stage4 at 39years. The variants detected were NPHP4 (NM_015102.3)c.1998_1999del;p.(Tyr667Phefs*23) and c.3646G>T;p.(Asp1216Tyr); ACMG Classes5 and 3 respectively. The latter variant was located in one of 4gaps in previous diagnostic sequencing of NPHP4 (94.3% exonic coverage).
Conclusions: Here we identify NPHP4 as an appreciable genetic cause for adult-diagnosed non-syndromic nephronophthisis. This gene should be considered by adult nephrologists with the aim of improving genomic translation in nephrology.


Biography:
After finishing medical school and her internship in Western Australia, Rebecca has worked at the Royal Brisbane and Women’s hospital since 2015, and has completed two rotations in Nephrology as a Resident and Registrar. She has thoroughly enjoyed this time both on the wards and in the dialysis unit, whilst also visiting external sites such as North Lakes and Redcliffe Hospital as a visiting Registrar. Currently in her 3rd year of Basic Physician Training, Rebecca is passionate about Nephrology and is committed to a high standard of care in this field going forward in her career.

GENETIC RENAL DISEASE IN TASMANIA

G BRAILSFORD1, E CASH1,  J BURKE3,  AJ MALLETT4,5,6, G KIRKLAND1,2,  M JOSE1,2
1School Of Medicine, University Of Tasmania, Hobart, Australia, 2Renal Unit, Royal Hobart Hospital, Hobart, Australia, 3Tasmanian Clinical Genetics Service, Hobart, Australia, 4Department of Renal Medicine, RBWH, Herston, Australia, 5Faculty of Medicine, The University of Queensland, Herston, Australia, 6KidGen Collaborative Australian Genomics Health Alliance, Parkville, Australia

Background: Genetic aetiology comprises a significant proportion of adults with chronic kidney disease (CKD) who develop end-stage kidney disease (ESKD) and experience an excess of morbidity and mortality.
Aim: To establish the prevalence of genetic renal disease (GRD) in Tasmania.
Methods: Individuals with GRD in Tasmania were identified from AUDIT4 (renal unit clinical database, n=2407) and ANZDATA (Australia and New Zealand Dialysis and Transplantation Registry, n=361) from 1st January 2012. After discarding duplicates, 2434 individuals referred to tertiary renal services were reviewed.
Results: In Tasmania, GRD comprised 8.5% of the CKD population (208/2434). GRD patients were younger than non-GRD patients (mean 52y vs. 64y, p <0.001). There was no significant difference in gender or mean eGFR between cohorts. Since 2012, GRD patients have more commonly developed ESKD, commenced RRT and received transplants than non-GRD patients (40% vs. 17%, p<0.001; 39.4% vs. 12.3% p<0.001; 30.3% vs. 5% p<0.001). Furthermore, GRD patients commenced RRT at a younger age (mean 46y vs 55y, p<0.001).
Of the GRD cohort, there was no significant difference in gender. Cystic kidney disease was the most common GRD (48%), followed by CAKUT (37%). Patients with CAKUT started RRT younger than those with cystic disease (mean 39y vs. 55y, p<0.001). Those who received transplants did so earlier (mean 36y vs. 52y, p<0.001). Patients with Glomerular, Tubular/Metabolic or other uncommon GRDs were more likely to be older males. Few GRD patients were known to the Tasmanian clinical genetics service, had undergone genetic testing or recieved counselling.
Conclusions: GRD constitutes a significant proportion of CKD in Tasmania. This data supports the development of a tailored genetic renal service for affected individuals.


Biography:
Gabrielle is a final year medical student at the University of Tasmania.

BEDSIDE TEST FOR DEFICIENT PERIPHERAL WARMTH PERCEPTION: A COMMON AND EARLY SIGN IN FABRY DISEASE

B NEDANOVSKI1, A TALBOT1, K NICHOLLS1,2
1The Royal Melbourne Hospital Department of Nephrology, Melbourne, Australia, 2The University of Melbourne, Melbourne, Australia

Aims: To determine
1. Prevalence and severity of sensory neuropathy in Fabry patients using simple bedside examination
2. Effect of enzyme replacement therapy
Background: Fabry disease is an X-linked lysosomal storage disorder that is associated with early mortality. Patients typically present in the first two decades of life with acroparaesthesia and heat intolerance. Time to diagnosis can be up to 20 years. Increased warmth detection threshold is often overlooked, with course and response to enzyme replacement therapy (ERT) poorly documented.
Method: Patients undergo serial neurologic examination 6-12 monthly, comprising lower and upper limb (LL/UL) stimuli (pin prick/cotton wool/heat probe), touched to the knee/elbow as reference, then to distal extremities and moved proximally until perceived as equal to the reference. Analgesia level was arbitrarily scored: none=0, toetips/fingertips=1, interphalangeal joint toe/DIPJ=2 …knee/elbow=10.
Sealed water containers provided heat (700C).
t-testing was used for analysis.
Results: In 118 patients (68 females) at baseline, symmetrical LL deficit in warmth perception was commoner than light touch and pain (89%vs38%vs33%). Seven patients <20yrs demonstrated a similar pattern (86% vs29%vs0%). UL deficits were similar (79.7% vs 38%vs31%).
Deficit severity (mean+/-SEM) was
(LL 4.1±0.3vs0.96±0.2vs1.4±0.2, UL 2.4±0.2vs0.9±0.2vs1.1±0.2, p<0.0001). Over time, in 70 untreated patients (51 females), deficit in warmth perception progressed in all limbs (p<0.01 at 5-10yrs and >10yrs). In 24 patients (20 males) started on ERT, deficit improved at 0.5-1 years (p=0.01) and did not progress thereafter.
Conclusion: Heat perception deficit is common, often isolated, increases over time and responds to ERT. Bedside testing may flag young patients for Fabry screening.


Biography:
Graduated Science with Honours in 2010 from the University of Melbourne and Walter and Eliza Institute of Medical Research. Graduated Doctor of Medicine from the University of Melbourne in 2015. Is currently a physician trainee at the Royal Melbourne Hospital.

HEREDITARY LEIOMOYOMATOSIS AND RENAL CELL CARCINOMA SYNDROME (HRLCC): AN EFFECTIVE MULTIDISCIPLINARY APPROACH TO A HEREDITARY RENAL CANCER PREDISPOSING SYNDROME

M AL-SHINNAG1,2
1Kidney Health Service, Royal Brisbane And Women’s Hospital , Herston, Australia, 2University of Queensland, Herston, Australia

Background: HLRCC is an autosomal dominant disorder caused by FH mutations characterized by skin piloleiomyomas, uterine leiomyomas and RCC. The cumulative risk of RCC is 10-16% with mean age at first RCC diagnosis of 41years. Life-long RCC screening recommended.
Aim: To assess adherence to surveillance guidelines in an Australian HLRCC cohort, and to describe disease characteristics.
Method: All patients with a diagnosis (clinical/genetic) of HLRCC at RBWH from 01/01/2014-31/12/2017 were included (HREC/17/QRBW/276). All patients were assessed and counselled by a Clinical Geneticist then referred to an Adult Nephrologist. Baseline and incident clinical variables were extracted and analysed.
Results: 22 patients were identified with median age of 57years. 16/22 were female. The median and cumulative follow-up time were 2 and 37years respectively. 7/22 had Chronic Kidney Disease. Cutaneous leiomyoma were noted in 15/22, cutaneous leiomyosarcoma in 1/22, and uterine fibroids in 10/16 female patients.
RCC was diagnosed in 1/22 during surveillance (age 47years) with a second patient awaiting surgical intervention for potential RCC (age 66years). 4/22 had RCC diagnosed prior to commencement of surveillance (ages 11-43years) with 3/4 being from the same family.  Surveillance MRI occurred in 19/22 patients, 1/22 was lost to follow up before first MRI, 1/22 is yet to have first MRI and 1/22 has experienced logistic difficulties due to residing in a rural setting. 18/22 patients have regular annual review. Of the remaining, 2/4 have been lost to follow up and 2/4 have been onward referred for follow up by their regional renal service
Conclusion: Evidence-based RCC screening is feasible and able to identify incident renal lesions. Multidisciplinary patient management enables expedited genetic counselling, diagnosis, longitudinal screening and RCC management.


Biography:
Mohammad Al-shinnag is a Basic Physician Trainee who is currently working in Queensland Health. He has strong interest in clinical genetics. Mohammad Graduated from School of Medicine , Jordan University of Science and Technology in 2008 and moved to Brisbane, Australia in 2011 to start his Journey in clinical training

BIRT HOGG DUBÉ SYNDROME (BHD): AN EFFECTIVE MULTIDISCIPLINARY APPROACH TO A HEREDITARY RENAL CANCER PREDISPOSING SYNDROME

M Al-SHINNAG1, H MARFAN2,3, R SUSMAN2,3, J WAKELING3,  S WOOD4,  AJ MALLETT1,2
1Kidney Health Service, Royal Brisbane And Women’s Hospital , Herston, Australia, 2Faculty of Medicine, The University of Queensland, Herston, Australia, 3Genetic Health Queensland, Herston, Australia, 4Department of Urology, Princess Alexandra Hospital, Woolloongabba , Australia

Background: BHD is a rare autosomal dominant disorder caused by germline FLCN mutations characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and Renal Cell Carcinoma (RCC). The cumulative risk of RCC is 16% with life-long screening recommended.
Aim: To assess adherence to surveillance guidelines in an Australian BHD cohort and to describe disease characteristics.
Method: All patients with a diagnosis (clinical/genetic) of BHD at RBWH 01/01/2014-31/12/2017 were included (HREC/17/QRBW/276). All patients were initially assessed and counselled by a Clinical Geneticist and Genetic Counsellor and then referred to an Adult Nephrologist. Baseline and incident clinical variables were extracted and analysed.
Results: 18 patients were identified with a median age of 57years. 9/18 were female. The median and cumulative follow-up time were 1.5years and 39years respectively.Cutaneous fibrofolliculoma was noted in 8/18 patients, lung cysts in 3/18 patients, spontaneous pneumothorax in 3/18 patients, and past parotid oncocytoma in 2/18. A positive family history was documented in 12/18 patients and 13/18 patients had a confirmed genetic diagnosis.Chest X-ray or computed tomography was undertaken in 13/18 patients. Surveillance magnetic resonance imaging occurred in 13/18 patients, initially annually and now third yearly. The remaining 5/18 patients who had not undertaken surveillance imaging :3/5 yet to have MRI and 2 lost follow up 2/18 patients have been diagnosed with RCC at the ages of 73 and 77years, both occurring prior to commencing surveillance. No RCC events have occurred whilst under surveillance, however 2/18 are undergoing intensified imaging for renal lesions of uncertain significance.
Conclusion: Coordinated screening and longitudinal care for BHD via multidisciplinary collaboration is feasible, with especial attention warranted for surveillance guideline adherence.


Biography:
Mohammad Al-shinnag is a Basic Physician Trainee who is currently working in Queensland Health. He has strong interest in clinical genetics. Mohammad Graduated from School of Medicine , Jordan University of Science and Technology in 2008 and moved to Brisbane, Australia in 2011 to start his Journey in clinical training.

12

About ANZSN

The ASM is hosted by Australian and New Zealand Society of Nephrology.

The aims of the Society are to promote and support the study of the kidney and urinary tract in health and disease, and to ensure the highest professional standards for the practice of nephrology in Australia and New Zealand.

Conference Managers

Please contact the team at Conference Design with any questions regarding the Annual Scientific Meeting

© 2015 - 2016 Conference Design Pty Ltd