Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders

Copeland, Harriet, Low, Karen J., Wynn, Sarah L., Ahmed, Ayesha, Arthur, Victoria, Balasubramanian, Meena, Bennett, Katya, Berg, Jonathan, Bertoli, Marta, Bryson, Lisa, Bucknall, Catrin, Campbell, Jamie, Chandler, Kate, Chauhan, Jaynee, Clarkson, Amy, Coles, Rachel, Conti, Hector, Costello, Philandra, Coupar, Tessa, Craig, Amy, Dean, John, Dillon, Amy, Dixit, Abhijit, Drew, Kathryn, Eason, Jacqueline, Forzano, Francesca, Foulds, Nicola, Gardham, Alice, Ghali, Neeti, Green, Andrew, Hanna, William, Harrison, Rachel, Hegarty, Mairead, Higgs, Jenny, Holder, Muriel, Irving, Rachel, Jain, Vani, Johnson, Katie, Jolley, Rachel, Jones, Wendy D., Jones, Gabriela, Joss, Shelagh, Kalinauskiene, Ruta, Kanani, Farah, Kavanagh, Karl, Khan, Mahmudur, Khan, Naz, Kivuva, Emma, Lahiri, Nayana, Lakhani, Neeta, Lampe, Anne, Lynch, Sally Ann, Mansour, Sahar, Marsden, Alice, Massey, Hannah, McKee, Shane, Mohammed, Shehla, Naik, Swati, Nesarajah, Mithushanaa, Newbury-Ecob, Ruth, Osborne, Fiona, Parker, Michael J., Patterson, Jenny, Pottinger, Caroline, Prapa, Matina, Prescott, Katrina, Quinn, Shauna, Radley, Jessica A., Robart, Sarah, Ross, Alison, Rosti, Giulia, Sansbury, Francis H., Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Shears, Debbie, Smithson, Sarah, Stewart, Helen, Suri, Mohnish, Tadros, Shereen, Theobald, Rachel, Thomas, Rhian, Tsoulaki, Olga, Vasudevan, Pradeep, Rodriguez, Maribel Verdesoto, Vittery, Emma, Whyte, Sinead, Woods, Emily, Wright, Thomas, Zocche, David, Firth, Helen V. and Wright, Caroline F. 2024. Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders. Genetics in Medicine Open 2 , 101864. 10.1016/j.gimo.2024.101864

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Abstract

Purpose We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study. Methods Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion (n = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision. Results Outcomes were recorded for 4237 diagnosed probands (85% of those eligible) from all 24 recruiting centers across the United Kingdom and Ireland. Clinical management was reported to have changed in 28% of affected individuals. Where individual-level interventions were recorded, additional diagnostic or screening tests were started in 903 (21%) probands through referral to a range of different clinical specialties, and stopped or avoided in a further 26 (0.6%). Disease-specific treatment was started in 85 (2%) probands, including seizure-control medications and dietary supplements, and contra-indicated medications were stopped or avoided in a further 20 (0.5%). The option of prenatal/preimplantation genetic testing was discussed with 1204 (28%) families, despite the relatively advanced age of the parents at the time of diagnosis. Importantly, condition-specific information or literature was given to 3214 (76%) families, and 880 (21%) were involved in family support groups. In the most common condition (KBG syndrome; 79 [2%] probands), clinical interventions only partially reflected the temporal development of phenotypes, highlighting the importance of consensus management guidelines and patient support groups. Conclusion Our results underscore the importance of achieving a clinico-molecular diagnosis to ensure timely onward referral of patients, enabling appropriate care and anticipatory surveillance, and for accessing relevant patient support groups.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
ISSN:	2949-7744
Date of First Compliant Deposit:	5 February 2025
Date of Acceptance:	20 June 2024
Last Modified:	07 Feb 2025 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/175935

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