BSPED2024 Oral Communications Endocrine Oral Communications 1 (9 abstracts)
Diagnostic testing using gene panels for severe childhood growth failure and multiple pituitary hormone deficiency in England
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: A genetic cause is found in up to 40% of children presenting with severe short stature and 30% with multiple pituitary hormone deficiency (MPHD) in selected cohorts. Since 2020, to inform diagnosis and tailor management, clinicians may access gene panels provided by three NHS England genomic laboratory hubs (GLHs) as part of the Genomic Medicine Service in England for short stature management: 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: deficiency of ≥2 pituitary hormones of neonatal/childhood-onset). The diagnostic yield and use of these panels by clinicians is unclear.
Methods: Data from R147 and R159 panels were reviewed from laboratories in two GLHs (Exeter and West Midlands) from 2020 to present. The diagnostic yield was defined as genetic variants classed as “likely pathogenic” or “pathogenic” using the American College of Medical Genetics & Genomics and Association of Clinical Genomic Science guidelines. Abbreviated patient postcodes were collected to determine panel usage by each GLH geographical area.
Results: 871 patients had R147 panel testing and 235 patients had R159 panel testing across both GLHs. Diagnostic yield for R147 was 8.0% (70/871): PTPN11 (n = 28, 3.2%); ACAN (n = 7, 0.8%); CCDC8 (n = 5, 0.6%); FGFR3 (n = 5, 0.6%); IGF1R (n = 3, 0.3%); PLAG1 (n = 3, 0.3%); OBSL1, RIT1, SOS1 (n = 2, 0.2% for each); ANKRD11, BRAF, CUL7, FANCA, GH1, GHR, HMGA2, MAP2K1, MAP2K2, NPR2, SHOC2, SOX3, SRCAP1 (n = 1, 0.1% for each). Diagnostic yield for R159 was 7.7% (18/235): PROP1 (n = 6, 2.6%); FGFR1, GLI2, HESX1, IGSF1, (n = 2, 0.9% for each); CHD7, GNRHR, OTX2, POU1F1 (n = 1, 0.4% for each). Significant variability in panel requests across geographical areas covered by GLHs was found.
Conclusions: PTPN11 and PROP1 were the most frequent gene changes identified by the short stature and MPHD panels respectively. Diagnostic yields for both gene panels was low. Although real-world utility of both gene panels was low, clinicians should remain aware of the benefits of gene panel testing. Strategies are needed to increase gene panel usage, refine eligibility criteria and improve panel diagnostics for childhood short stature and MPHD disorders.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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