Original Title: Utilidad de la secuenciación del exoma en el diagnóstico de dismorfias con o sin discapacidad intelectual. Revisión de la literatura

Authors' objectives: Our scope was to establish the clinical utility of exome sequencing in terms of diagnostic performance in patients under 18 with dismorphic syndromes, with or without intellectual disabilities. Specifically, we proposed the creation of a map of evidence, the calculation of the diagnostic performance of the test as well as the identification of the most relevant ethical and organizational implications.

Authors' results and conclusions: The literature retrieved for this review has been mostly composed of single patient case series studies, which have a low level of evidence. The quality of the studies is directly related to the sample size studied.. The exact diagnostic yield of exoma sequencing in minors with dysmorphia, with or without intellectual developmental disorder, is unknown. From the review, a diagnostic yield of approximately 30 % is extracted, dropping to 21 % in the work considered of higher quality. The best results were obtained in patients who had some of the following conditions: they belonged to inbred families, had disorders in intellectual development, had a parent with a similar phenotype or showed an inherited dominant or X-linked pattern. There are no rigorous comparisons of the effectiveness of complete exome sequencing with respect to traditional diagnostic methods, although published data would indicate a slight superiority of this technology over standard techniques. Approximately 10 % of the patients with positive results established a genetic diagnosis that changed the initial one or modified the diagnosis of suspicion. The test has shown its usefulness in establishing new associations between genes and phenotypes or in increasing the phenotypic spectrum of previously defined clinical entities. The reviewed literature does not allow us to know relevant aspects of clinical validity as its sensitivity, specificity and predictive values, uncertainty regarding its clinical utility is also maintained. Moreover, it doesn´t allow us to draw conclusions related to the impact on patient care, effectiveness, unwanted effects of its use, impact on the care process, or its cost-effectiveness. Exome sequencing may be useful in patients with rare, clinically and genetically heterogeneous diseases as well as atypical or non-specific presentation. Our study demonstrates the clinical utility of the complete exome analysis in clinical research areas and contributes to knowledge of the genetic origin of certain diseases and the extension of its genetic spectrum. From an ethical point of view, the main concern in the reviewed literature, is the communication of the main results and the management of the secondary findings. Informed consent for complete exome sequencing generally has particularities and therefore the usual recommendations may be insufficient.

Authors' methods: A structured review of the literature has been carried out following the recommendations of the PRISMA statement. To this end, we consulted the Medline (OVID, PubMed), Embase and Web of Science databases up until March 2016. The selection, evaluation and extraction of data was carried out by two independent researchers. The risk of bias for a particular type of study and evidence level was evaluated using the OSTEBA criteria for case series. The EpiInfo v7.2 software was used for tabulation of data and statistical calculations.

Project Status: Completed

Year Published: 2017

URL for published report: https://www.aetsa.org/publicacion/utilidad-de-la-secuenciacion-del-exoma-en-el-diagnostico-de-dismorfias-con-o-sin-discapacidad-intelectual-revision-de-la-literatura/

Requestor: Health Ministry of Spain

English language abstract: An English language summary is available

Publication Type: Other

Country: Spain

Organisation Name: Andalusian Health Technology Assessment Area

Contact Address: Area de Evaluacion de Tecnologias Sanitarias Sanitarias de Andalucia (AETSA) Avda. Innovación, s/n Edificio Arena 1. Sevilla (Spain) Tel. +34 955 006 309

Contact Name: aetsa.csalud@juntadeandalucia.es

Contact Email: aetsa.csalud@juntadeandalucia.es

Copyright: AETSA, Andalusian Health Technology Assessment Area