Original Title: Revisión sistemática de los aCGH para el estudio genético de trastornos del neurodesarrollo en etapa pediátrica

Authors' objectives: Systematic review of scientific literatura about aCGH for the genetic study of the neurodevelopmental impairments in pediatric population.

Authors' results and conclusions: RESULTS: In this systematic review 84 papers were included. Six secondary studies, 73 primary studies and 3 economic evaluations were included. The number of subjects included in the studies varied between 20 and 15,767. The main results are the following: • In patients with MR/ID and negative karyotype, the rate of pathogenic copy number variants (CNV) varied between 5% and 26% for BAC-based aCGH and between 6% and 30% for oligonucleotide aCGH. The meta-analysis estimated a diagnosis yield rate of 10.5% for BAC-based aCGH and 14.3% for oligonucleotide aCGH. • In patients with ASD, the rates varied between 1.12% and 28%. Higher rates were found in patients with syndromic ASD or with MR/ID. • Few studies of diseases such as epilepsy, ADHS or specific síndromes were identified. • The economic evaluations, none of them conducted in Spain, concluded that aCGH is cost-effective for the genetic study of ID. CONCLUSIONS: • The aCGH is a technique that can identify pathogenic CNVs that are not detectable by means of the conventional karyotype in patients with MR/ID. The performance of BAC-based aCGH seems to be better than the performance of oligonucleotide aCGH. • There are some evidence of acceptable rates of aCGH for the study of ASD, epilepsy and ADHS. However, the limited number of studies prevent concluding about the performance of aCGH for these diseases. • Although the economic evaluations conducted abroad concluded that aCGH is a cost-effective technique for the genetic study of ID, a cost-effectiveness analysis from our National Health System point of view would be needed.

Authors' recommendations: Given the results and conclusions of this systematic review, the following recommendations are stated: • To consider aCGH as a potential substitute of the karyotype for the genetic study of ID/MR when this study is needed, relegating karyotype for those syndroms more easily recognizable. • The genetic study of other disorders with aCGH, like ASD, should be limited to some cases according the recommendations of clinical guidelines for those diseases. • A cost-effectiveness analysis of aCGH in comparison to other genetic techniques for the study of ID/MR should be conducted from the Spanish National Health System perspective.

Authors' methods: Systematic searches were made in electronic databases MEDLINE and MEDLINE in process, EMBASE, The Cochrane Library Plus (CENTRAL, Cochrane Systematic Reviews Database), PsycInfo and CRD (DARE, HTA, NHS-EED) in October 2014. References in previous systematic reviews were also revised. Studies that assessed the diagnostic yield of oligonucleotide aCGH or BAC-based aCGH for the genetic study of children and adolescents with neurological problems were included. Neurological problems included: learning disabilities, ID/MR, autism spectrum disorder (ASD), epilepsy, attention deficit hyperactivity disorder (ADHD), dismorphic traits, among others. Cost-effectiveness studies were also included. The studies were selected independently by two reviewers. The data extraction was carried out by a reviewer and checked by a second reviewer. The verification of compliance with the inclusion criteria was conducted by an economist and a physiotherapist. The two reviewers contrasted their views and when they had doubts or discrepancies, these were resolved by consensus or with the help of a third reviewer. The data were gathered in spreadsheets designed ad hoc. The methodological quality of the included studies was assessed. The data collected were synthesized through narrative procedures with detailed tables of the results. A meta-analysis of studies including patients with ID was conducted.

Project Status: Completed

Year Published: 2014

URL for published report: https://sescs.es/r-s-de-los-acgh-para-el-estudio-genetico-de-trastornos-del-neurodesarrollo-pediatrico/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es