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

ABSTRACT Objective We sought to evaluate outcomes for clinical management following a genetic diagnosis from the Deciphering Developmental Disorders (DDD) Study. Design Individuals in the DDD 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 pre-defined 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 centres across the UK and Ireland. Additional diagnostic or screening tests were performed 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/avoided as no longer necessary 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. Conclusions 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.