Fig. 3

Algorithm in patients with unexplained ID and/or and/or ASD. After the collection of appropriate clinical and family history, you need to take a detailed physical and dysmorphology examination. If patient has a recognizable pattern of signs and symptoms you have to confirm diagnosis by cytogenetic or molecular targeted test. Nonetheless the infrequent detection rate Fragile X A/E syndrome should be excluded in all patients with ID. If the patient does not present with features of recognizable syndrome or metabolic disorder or the latter resulted negative for a suspected syndromes aCGH is the first-tier test especially in case of ASD diagnosis or family history positive for ID/MCA/ASD. Other potential predictors of pathogical results are: ocular anomalies, hearing loss, neurological signs, cutaneous dyscromia and endocrinological problems. If aCGH comes back negative further clinical investigations are warranted. If the detected CNV includes relevant region/genes or the gene content and its size meet guidelines criteria the result has to be considered pathogenic. In such cases parental studies and evaluation of cytogenetic feature as gene density could aid in ascertain their likely pathogenicity