Technological evolution in genomics has a very fast speed and clinical guidelines become obsolete with respect to usual clinical practice, so that professionals frequently find themselves with questions that are difficult to answer.
Much has happened since the 2003 AAN guidelines, in which the use of karyotyping and fragile X, currently withdrawn, was proposed as the first step in the study of global developmental delay and autism spectrum disorders. , after the review carried out in 2011 by the same authors .
The 2012 guidelines of the American Academy of Pediatrics introduced for the first time the systematic use of aCGH. . A not unexpected consequence has been the progressive decline of traditional cytogenetic techniques (karyotyping), to the point that the "know how" is being lost, and the number of professionals capable of performing the technique is at risk of extinction.
Since then, the appearance of exome sequencing studies has meant a revolution from the point of view of increasing diagnostic yield. In particular, the appearance of bioinformatic systems for detecting CNVs based on data obtained from exome sequencing has allowed us to seriously question the usefulness of performing a prior aCGH.
In the latest ACMG guidelines of 2021, it has been analyzed whether the exome should be the 1st step in the diagnostic study of patients with multiple congenital malformations and intellectual disability, proposing a change in the current paradigm.
However, there continues to be discussion in the field regarding what the current sequence of decisions should be from the point of view of clinical practice, timidly questioning whether it is really profitable to continue performing X-fragil on the entire population, given the decrease in prevalence identified in recent decades. .