Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness

Abstract

There are no guidelines available for diagnostic studies in patients with mental retardation (MR) established in an evidence-based manner. Here we report such study, based on information from original studies on the results with respect to detected significant anomalies (yield) of six major diagnostic investigations, and evaluate whether the yield differs depending on setting, MR severity, and gender. Results for cytogenetic studies showed the mean yield of chromosome aberrations in classical cytogenetics to be 9.5% (variation: 5.4% in school populations to 13.3% in institute populations; 4.1% in borderlinemild MR to 13.3% in moderate-profound MR; more frequent structural anomalies in females). The median yield of subtelomeric studies was 4.4% (also showing female predominance). For fragile X screening, yields were 5.4% (cytogenetic studies) and 2.0% (molecular studies) (higher yield in moderate-profound MR; checklist use useful). In metabolic investigations, the mean yield of all studies was 1.0% (results depending on neonatal screening programmes; in individual populations higher yield for specific metabolic disorders). Studies on neurological examination all showed a high yield (mean 42.9%; irrespective of setting, degree of MR, and gender). The yield of neuroimaging studies for abnormalities was 30.0% (higher yield if performed on an indicated basis) and the yield for finding a diagnosis based on neuroradiological studies only was 1.3% (no data available on value of negative findings). A very high yield was found for dysmorphologic examination (variation 39 -81%). The data from this review allow conclusions for most types of diagnostic investigations in MR patients. Recommendations for further studies are provided.

Aetiology of intellectual disability in paediatric outpatients in Northern India

“…This proportion of diagnostic success compares well with studies conducted in wellequipped Western centres, where it has varied from 27 to 61%. 7,[27][28][29] Some of these studies have focused only on 'idiopathic' intellectual disability or GDD, which would explain the lower yield. Others have included all children presenting with intellectual disability or GDD, but settings such as theirs are likely to have a higher proportion of genetic cases.…”

“…Others have included all children presenting with intellectual disability or GDD, but settings such as theirs are likely to have a higher proportion of genetic cases. [27][28][29] Genetic and chromosomal causes are difficult to diagnose without sophisticated tests.…”

“…Previous studies have shown widely variable yield of cytogenetic investigations. 28 Clinicians who have found dysmorphic features as predictive of reaching an aetiological diagnosis have employed more sophisticated techniques for diagnosis. 5 A higher yield and a positive association of dysmorphology with successful aetiologic diagnosis may have been obtained by employing these, or more sophisticated tests like fluorescence in situ hybridization for submicroscopic subtelomeric rearrangements, and array comparative genomic hybridization.…”

Medical Comorbidities in Autism: Challenges to Diagnosis and Treatment

“…Among this population, the estimated diagnostic yield has been found to vary between 1% to 2.5%. 27 In a more recent study, Engbers et al 28 performed repeated metabolic analyses on a cohort of 433 subjects with neurodevelopmental impairments, whose initial evaluations were said to be unremarkable. Of these subjects, 12 (2.8%) were found to have diagnostic disorders, some of which were treatable.…”

Diagnostics: Genomic copy number analysis in mental retardation: finding the needles in the haystack

“…The diagnostic yield of these approaches in the general population of patients with unexplained mental retardation is approximately 10%. 1 Thanks to the human genome sequencing project and the development of microarray-based genome profiling methods such as array-based comparative genomic hybridization (array CGH 2 ), we are now able to screen the human genome for the presence of genomic dosage variations at an unprecedented resolution. These methods will rapidly find their way in novel diagnostic applications if validation and clinical interpretation become straightforward.…”