Diagnostic yield of microarrays in individuals with non-syndromic developmental delay and intellectual disability

Intellectual disability (ID), or developmental delay (DD) when the individual is yet under 5 years of age, is evident before 18 years of age and is characterised by significant limitations in both intellectual functioning and adaptive behaviour. ID/DD may be clinically classified as syndromic or non-syndromic. Genomic copy number variations (CNVs) constitute a well-established aetiological subgroup of ID/DD. Overall diagnostic yield of microarrays is estimated at 10-25% for ID/DD, especially higher when particular clinical features that render the condition syndromic accompany.

In this study, we aimed to investigate the diagnostic yield of microarrays in the subgroup of individuals with non-syndromic ID/DD (NSID/NSDD). A total of 302 NSID/NSDD individuals who have undergone microarray analysis between October 2013 and April 2020 were included. Accompanying clinical data, including head circumference, delayed developmental areas, seizures and behavioural problems were collected and analysed separately in NSID and NSDD subgroups.

The diagnostic yield of microarray analyses in NSID/NSDD was determined as 10.9% in NSID (10.7%) and in NSDD (11.1%). Presence of behavioural and epileptic problems did not contribute to the diagnostic yield. However, in the presence of macrocephaly, the contribution to diagnostic yield was statistically significant particularly in NSDD group. The most common pathogenic CNVs involved chromosomes 16, 15 and X. Lastly, we propose a Xq21.32q22.1 deletion as likely pathogenic in a child with isolated language delay and accompanying seizures.

Particularly in neurodevelopmental diseases, microarrays are useful for establishing the diagnosis and detecting novel susceptibility regions. Future studies would accurately classify the herein presented variants of uncertain significance CNVs as pathogenic or benign.