Large-scale evaluation of outcomes following a genetic diagnosis in children with severe developmental disorders
Authors: Copeland Harriet , Low Karen J , Wynn Sarah , 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 Nicky , 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 , Jones Gabriela , Joss Shelagh , Kalinauskiene Ruta , Kanini 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 , Sarkar Ajoy , Searle Claire , Shannon Nora , Shears Debbie , Smithson Sarah , Stewart Helen , Suri Mohnish , Tadros Shereen , Theobald Rachel , Thomas Rhian , Tsoulaki Olga , Vasudevan Pradeep , Verdesoto Maribel , Vittery Emma , Whyte Sinead , Woods Emily , Wright Thomas , Zocche David , Firth Helen V , Wright Caroline F 
Published: October 2023

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.