Predictive diagnostic value for the clinical features accompanying intellectual disability in children with pathogenic copy number variations: a multivariate analysis

Abstract

Background: Array comparative genomic hybridization (a-CGH) has become the first-tier investigation in patients with unexplained developmental delay/intellectual disability (DD/ID). Although the costs are progressively decreasing, a-CGH is still an expensive and labour-intensive technique: for this reason a definition of the categories of patients that can benefit the most of the analysis is needed. Aim of the study was to retrospectively analyze the clinical features of children with DD/ID attending the outpatient clinic of the Mother & Child Department of the University Hospital of Modena subjected to a-CGH, to verify by uni- and multivariate analysis the independent predictors of pathogenic CNVs.

Methods: 116 patients were included in the study. Data relative to the CNVs and to the patients' clinical features were analyzed for genotype/phenotype correlations.

Results and conclusions: 27 patients (23.3%) presented pathogenic CNVs (21 deletions, 3 duplications and 3 cases with both duplications and deletions). Univariate analysis showed a significant association of the pathogenic CNVs with the early onset of symptoms (before 1 yr of age) and the presence of malformations and dysmorphisms. Logistic regression analysis showed a significant independent predictive value for diagnosing a pathogenic CNV for malformations (P = 0.002) and dysmorphisms (P = 0.023), suggesting that those features should address a-CGH analysis as a high-priority test for diagnosis.

Figure 1

Clinical features of the patients under study according to the presence of pathogenic CNVs. For each variable the number (n=), the percentage of patients (in parenthesis) and the P values (in boxes) are reported. Statistical significance is indicated with the presence of an asterisk.