The Andalusian Agency for Health Technology Assessment released an evaluation report on the utility of exome sequencing for diagnosed dysmorphic syndromes

Mass sequencing techniques (NGS) and especially exome sequencing have demonstrated to be diagnostic tools that have awaken much interest. Despite that, there were difficulties about incorporating this diagnosis tool into everyday procedures because of the importance and management of the information in some cases. The evaluation of this diagnosis tool was prioritized by Portfolio Committee of the Spanish National Health Service (SNS) and was included in the Spanish Network for HTA Plans in 2016.

Key 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”

See the full report in Spanish with English summary here.

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