Submicroscopic Chromosomal Variations in Children With Idiopathic Intellectual and Developmental Disabilities

Abstract

Objective: Intellectual disability is the most common developmental disorder that originates before the age of 18 years and is characterized by limitation in intellectual functioning and adaptive behaviour. The fact that >30 to 50% of all causes are still unknown in etiology is increasing the burden of the clinical evaluators and managers handling these children. The purpose of this study was to have an optimal genetic diagnostic evaluation to assist paediatricians in providing medical advice for children with intellectual disabilities and global developmental delays.
 Methods: The study was initiated with 385 cases; however, only 201 cases had no cytogenetic abnormality and negative for PCR test for FXS. However, these subjects showed characteristic signs of facial dysmorphisms, developmental delay, mild to severe intellectual disability, which were unique and unspecific with lack of major hallmarks for any particular syndrome/phenotype, considered as “idiopathic” and tested for MLPA analysis and subsequently confirmed by FISH and RT-qPCR.
 Results: A total of 23 (11.44%) cases were found to have submicroscopic chromosomal variations [microdeletions (18 cases), microduplications (5 cases)]. We categorized the aberrations detected in these cases as novel and as variants of uncertain significance. All these cases showed clear evidence for segregation of the variation and were provided with the required genetic counselling.
 Conclusion: MLPA method gives a better yield in combination with karyotype analysis. The detection rate as per current analysis suggests that the use of MLPA could be a robust, high throughput yet cost-effective technique for use in a diagnostic set up.