ESPE2024 Poster Category 1 Growth and Syndromes 2 (10 abstracts)
Real-world utility of diagnostic gene panels for severe childhood growth failure and multiple pituitary hormone deficiency in the UK
David BN Lim 1 , Louise McCelland 2 , Suzanne Page 3 , Melissa Connolly 2 , Martina Owens 3 , Chris Bowles 3 , Helena Palau 4 , Avinaash V Maharaj 4 , Miho Ishida 4 , Helen L Storr 4 & Justin H Davies 1,5
1Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 2Central and South Genomic Laboratory Hub, Birmingham Women’s and Children NHS Foundation Trust, Birmingham, United Kingdom. 3Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom. 4Centre for Endocrinology, William Harvey Research Institute, Charterhouse Square, Barts and the London School of Medicine, London, United Kingdom. 5Faculty of Medicine, University of Southampton, Southampton, United Kingdom
Background: In selected cohorts, a genetic cause is found in up to 40% of children presenting with severe short stature (height <-3 SDS) and 30% with multiple pituitary hormone deficiency (MPHD). Since 2020, to inform diagnosis and tailor management, three NHS England genomic laboratory hubs (GLHs) have offered clinicians access to gene panels as part of routine care for short stature: R147 ‘Growth failure in early childhood’ (eligibility: height/length <-3 SDS at age >2 years and/or clinical features indicative of Silver-Russell syndrome) and R159 ‘Pituitary hormone deficiency’ (eligibility: at least two pituitary hormones childhood-onset). The diagnostic yield and use of these panels by clinicians is unclear.
Methods: From 2020, data from R147 and R159 panels were reviewed from two GLHs (Exeter and West Midlands). Variants were classified using the American College of Genetics and Genomics guidelines. The positive diagnostic yield was defined as genetic variants classed as 'likely pathogenic' or 'pathogenic'. Panel usage by each GLH geographical area was ascertained using abbreviated patient postcodes.
Results: Panels analysed: 340 (Exeter; R147 n = 268 and R159 n = 72) and 766 (West Midlands; R147 n = 603 and R159 n = 163). Diagnostic yield R147: Exeter 6.7%; West Midlands 8.6%. Diagnostic yield R159: Exeter 9.7%; West Midlands 6.7%. Positive diagnoses R147: Exeter: PTPN11 (n = 5); ACAN (n = 2); PLAG1, ANKRD11, BRAF, CCDC8, CUL7, FANCA, FGFR3, IGFR1, MAP2K1, MAP2K2, OBSL1 (n = 1 each). West Midlands: PTPN11 (n = 23); ACAN (n = 5); CCDC8 (n = 4); FGFR3 (n = 4); IGF1R (n = 2); PLAG1 (n = 2); RIT1 (n = 2); SOS1 (n = 2); GH1, GHR, HMGA2, NPR2, OBSL1, SHOC2, SOX3, SRCAP (n = 1 each). Positive diagnoses R159 : Exeter: PROP1 (n = 2); HESX1 (n = 2); GLI2 (n = 2); IGSF1 (n = 1). West Midlands: PROP1 (n = 4); FGFR1 (n = 2); CHD7, GNRHR, IGSF1, OTX2, POU1F1 (n = 1 each). Panel utility: There was considerable variability in panel usage across geographical areas with large areas of the UK not accessing these investigations.
Conclusions: In a real-world setting there was a low diagnostic yield (<10%) for both gene panels. There was poor uptake in sizeable areas of the UK where gene panels were not requested despite high population density. PTPN11 and PROP1 were the commonest gene changes detected by the short stature and MPHD panels, respectively. Strategies are needed to improve gene panel usage, refine eligibility criteria, and enhance panel diagnostics for childhood short stature and MPHD disorders. A rationalised approach to the available genetic testing strategies could address some of these issues.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more