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

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.; Lampe, A.; Lynch, SA.; Mansour, S.; Marsden, A.; Massey, H.; McKee, S.; Mohammed, S.; Naik, S.; Nesarajah, M.; Newbury-Ecob, R.; Osborne, F.; Parker, MJ.; Patterson, J.; Pottinger, C.; Prapa, M.; Prescott, K.; Quinn, S.; Radley, JA.; Robart, S.; Ross, A.; Rosti, G.; Sansbury, FH.; Sarkar, A.; Searle, C.; Shannon, N.; Shears, D.; Smithson, S.; Stewart, H.; Suri, M.; Tadros, S.; Theobald, R.; Thomas, R.; Tsoulaki, O.; Vasudevan, P.; Rodriguez, MV.; Vittery, E.; Whyte, S.; Woods, E.; Wright, T.; Zocche, D.; Firth, HV.; Wright, CF.

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

All Authors

Copeland, H.

Low, KJ.

Wynn, SL.

Ahmed, A.

Arthur, V.

Balasubramanian, M.

Bennett, K.

Berg, J.

Bertoli, M.

Bryson, L.

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LTHT Author

Chauhan, Jaynee
Prescott, Katrina

LTHT Department

Pathology
Clinical Genetics
Yorkshire Regional Genetics Service

Publication Date

2024

Item Type

Journal Article

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.