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

Harriet Copeland; Karen J. Low; Sarah L. Wynn; Ayesha Ahmed; Victoria Arthur; Meena Balasubramanian; Katya Bennett; Jonathan Berg; Marta Bertoli; Lisa Bryson; Catrin Bucknall; Jamie Campbell; Kate Chandler; Jaynee Chauhan; Amy Clarkson; Rachel Coles; Hector Conti; Philandra Costello; Tessa Coupar; Amy Craig; John Dean; Amy Dillon; Abhijit Dixit; Kathryn Drew; Jacqueline Eason; Francesca Forzano; Nicola Foulds; Alice Gardham; Neeti Ghali; Andrew Green; William Hanna; Rachel Harrison; Mairead Hegarty; Jenny Higgs; Muriel Holder; Rachel Irving; Vani Jain; Katie Johnson; Rachel Jolley; Wendy D. Jones; Gabriela Jones; Shelagh Joss; Ruta Kalinauskiene; Farah Kanani; Karl Kavanagh; Mahmudur Khan; Naz Khan; Emma Kivuva; Nayana Lahiri; Neeta Lakhani; Caroline F. Wright

doi:10.1016/j.gimo.2024.101864

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

Harriet Copeland
, Karen J. Low
, Sarah L. Wynn
, Ayesha Ahmed
, Victoria Arthur
, Meena Balasubramanian
, Katya Bennett
, Jonathan Berg
, Marta Bertoli
, Lisa Bryson
, Catrin Bucknall
, Jamie Campbell
, Kate Chandler
, Jaynee Chauhan
, Amy Clarkson
, Rachel Coles
, Hector Conti
, Philandra Costello
, Tessa Coupar
, Amy Craig

John Dean, Amy Dillon, Abhijit Dixit, Kathryn Drew, Jacqueline Eason, Francesca Forzano, Nicola Foulds, Alice Gardham, Neeti Ghali, Andrew Green, William Hanna, Rachel Harrison, Mairead Hegarty, Jenny Higgs, Muriel Holder, Rachel Irving, Vani Jain, Katie Johnson, Rachel Jolley, Wendy D. Jones, Gabriela Jones, Shelagh Joss, Ruta Kalinauskiene, Farah Kanani, Karl Kavanagh, Mahmudur Khan, Naz Khan, Emma Kivuva, Nayana Lahiri, Neeta Lakhani, Caroline F. Wright (Lead / Corresponding author),

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

4 Downloads (Pure)

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.

Original language	English
Article number	101864
Number of pages	11
Journal	Genetics in Medicine Open
Volume	2
Early online date	27 Dec 2024
DOIs	https://doi.org/10.1016/j.gimo.2024.101864
Publication status	Published - 2024

Keywords

Clinical audit
Developmental disorders
Diagnosis
Genomic medicine
Treatment

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Molecular Biology
Genetics
Cell Biology

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10.1016/j.gimo.2024.101864Licence: CC BY

Final Published VersionFinal published version, 973 KBLicence: CC BY

Cite this

Copeland, H., Low, K. J., Wynn, S. L., Ahmed, A., Arthur, V., Balasubramanian, M., Bennett, K., Berg, J., Bertoli, M., Bryson, L., Bucknall, C., Campbell, J., Chandler, K., Chauhan, J., Clarkson, A., Coles, R., Conti, H., Costello, P., Coupar, T., ... Wellcome Sanger Institute (2024). Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders. Genetics in Medicine Open, 2, Article 101864. https://doi.org/10.1016/j.gimo.2024.101864

@article{f02771ee50e24461a13efc32242fa27a,

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

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.",

keywords = "Clinical audit, Developmental disorders, Diagnosis, Genomic medicine, Treatment",

author = "Harriet Copeland and Low, \{Karen J.\} and Wynn, \{Sarah L.\} and Ayesha Ahmed and Victoria Arthur and Meena Balasubramanian and Katya Bennett and Jonathan Berg and Marta Bertoli and Lisa Bryson and Catrin Bucknall and Jamie Campbell and Kate Chandler and Jaynee Chauhan and Amy Clarkson and Rachel Coles and Hector Conti and Philandra Costello and Tessa Coupar and Amy Craig and John Dean and Amy Dillon and Abhijit Dixit and Kathryn Drew and Jacqueline Eason and Francesca Forzano and Nicola Foulds and Alice Gardham and Neeti Ghali and Andrew Green and William Hanna and Rachel Harrison and Mairead Hegarty and Jenny Higgs and Muriel Holder and Rachel Irving and Vani Jain and Katie Johnson and Rachel Jolley and Jones, \{Wendy D.\} and Gabriela Jones and Shelagh Joss and Ruta Kalinauskiene and Farah Kanani and Karl Kavanagh and Mahmudur Khan and Naz Khan and Emma Kivuva and Nayana Lahiri and Neeta Lakhani and Wright, \{Caroline F.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

doi = "10.1016/j.gimo.2024.101864",

language = "English",

volume = "2",

}

Copeland, H, Low, KJ, Wynn, SL, Ahmed, A, Arthur, V, Balasubramanian, M, Bennett, K, Berg, J, Bertoli, M, Bryson, L, Bucknall, C, Campbell, J, Chandler, K, Chauhan, J, Clarkson, A, Coles, R, Conti, H, Costello, P, Coupar, T, Craig, A, Dean, J, Dillon, A, Dixit, A, Drew, K, Eason, J, Forzano, F, Foulds, N, Gardham, A, Ghali, N, Green, A, Hanna, W, Harrison, R, Hegarty, M, Higgs, J, Holder, M, Irving, R, Jain, V, Johnson, K, Jolley, R, Jones, WD, Jones, G, Joss, S, Kalinauskiene, R, Kanani, F, Kavanagh, K, Khan, M, Khan, N, Kivuva, E, Lahiri, N, Lakhani, N, Wright, CF & Wellcome Sanger Institute 2024, 'Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders', Genetics in Medicine Open, vol. 2, 101864. https://doi.org/10.1016/j.gimo.2024.101864

TY - JOUR

T1 - Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders

AU - Copeland, Harriet

AU - Low, Karen J.

AU - Wynn, Sarah L.

AU - Ahmed, Ayesha

AU - Arthur, Victoria

AU - Balasubramanian, Meena

AU - Bennett, Katya

AU - Berg, Jonathan

AU - Bertoli, Marta

AU - Bryson, Lisa

AU - Bucknall, Catrin

AU - Campbell, Jamie

AU - Chandler, Kate

AU - Chauhan, Jaynee

AU - Clarkson, Amy

AU - Coles, Rachel

AU - Conti, Hector

AU - Costello, Philandra

AU - Coupar, Tessa

AU - Craig, Amy

AU - Dean, John

AU - Dillon, Amy

AU - Dixit, Abhijit

AU - Drew, Kathryn

AU - Eason, Jacqueline

AU - Forzano, Francesca

AU - Foulds, Nicola

AU - Gardham, Alice

AU - Ghali, Neeti

AU - Green, Andrew

AU - Hanna, William

AU - Harrison, Rachel

AU - Hegarty, Mairead

AU - Higgs, Jenny

AU - Holder, Muriel

AU - Irving, Rachel

AU - Jain, Vani

AU - Johnson, Katie

AU - Jolley, Rachel

AU - Jones, Wendy D.

AU - Jones, Gabriela

AU - Joss, Shelagh

AU - Kalinauskiene, Ruta

AU - Kanani, Farah

AU - Kavanagh, Karl

AU - Khan, Mahmudur

AU - Khan, Naz

AU - Kivuva, Emma

AU - Lahiri, Nayana

AU - Lakhani, Neeta

AU - Wright, Caroline F.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Clinical audit

KW - Developmental disorders

KW - Diagnosis

KW - Genomic medicine

KW - Treatment

UR - https://www.scopus.com/pages/publications/85212392957

U2 - 10.1016/j.gimo.2024.101864

DO - 10.1016/j.gimo.2024.101864

M3 - Article

AN - SCOPUS:85212392957

VL - 2

JO - Genetics in Medicine Open

JF - Genetics in Medicine Open

M1 - 101864

ER -

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

Abstract

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