biostudies-literatureCopeland HNational Institute for Health Research (NIHR)Wellcome Trust101864https://www.ebi.ac.uk/biostudies/studies/S-EPMC11736166biostudies-literatureUnknown2<h4>Purpose</h4>We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.<h4>Methods</h4>Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion (<i>n</i> = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.<h4>Results</h4>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.<h4>Conclusion</h4>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.Genetics in medicine openLarge-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.PMC11736166NIHR203312NIHR302303226083/Z/22/ZTsoulaki OPatterson JMohammed SCopeland HChauhan JDillon ANaik SColes RWright TArthur VCoupar TWynn SLStewart HFoulds NJones WDOsborne FPrescott KHanna WWoods EDDD Study28Chandler KShears DWhyte SWright CFAhmed ACostello PEason JRosti GCraig AKivuva ESearle CLynch SAClarkson AForzano FGhali NFirth HVParker MJHiggs JHegarty MJain VVittery EKanani FJohnson KMarsden ABryson LHarrison RMansour SShannon NZocche DLow KJMassey HJones GKalinauskiene RTadros SRodriguez MVConti HRadley JAThomas RKavanagh KBertoli MGardham AMcKee SLampe APrapa MJolley RHolder MDixit AJoss SRoss ASarkar AVasudevan PQuinn SSmithson SGreen ASansbury FHBerg JBalasubramanian MRobart SPottinger CNesarajah MNewbury-Ecob RBennett KSuri MLahiri NBucknall CTheobald RCampbell JDrew KIrving RKhan MLakhani NKhan NDean JfalseLarge-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.<h4>Purpose</h4>We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.<h4>Methods</h4>Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion (<i>n</i> = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.<h4>Results</h4>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.<h4>Conclusion</h4>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.2024-01-01T00:00:00Z20242026-04-08T19:12:26.026Z2026-04-08T12:34:44.454ZS-EPMC117361663982226710.1016/j.gimo.2024.101864