Incidental findings in array CGH

Array Comparative Genomic Hybridization (array CGH) is nowadays widely used in the diagnostic work-up of intellectual disability, congenital anomalies and psychiatric disorders. In contrast with the standard karyotype, it allows us to pick up microdeletions - and duplications, thus increasing the number of patients for which the etiology of their problem can be demonstrated. In few cases, the array CGH result also uncovers susceptibility to serious late(r)-onset disorders, such as hereditary cancer syndromes. Although the risk for such an incidental finding is low, the physician who prescribes the analysis should be aware of this possibility and should inform the patient and/or the parents before the test is undertaken. In case of a parentally inherited aberration, the carrier parent is equally at risk for the concerned disorder and pretesting counseling should address this item too. We will illustrate the possibility of incidental findings on array CGH with two cases. The first patient is an infant with congenital anomalies and severe hypotonia. Array CGH analysis reveals a 23Mb deletion of 5q22.1q23.1. This region includes the APC gene, responsible for Familial Adenomatous Polyposis. This child will thus require close gastrointestinal follow-up from the age of 10 years on. Since the deletion is de novo, the parents are not at increased risk. The second patient is a girl with bilateral aniridia. She has a 15 Mb deletion on 11p14.1p11.2, encompassing the PAX 6 gene, which explains the ocular phenotype. However, the deletion also includes the WT1 gene, involved in renal neoplasia. Close monitoring allowed the early detection and treatment of a kidney tumor in the child. Conclusion: we want to draw the attention of the prescriber of array CGH to the small but existing risk of incidental findings with important consequences for the patient. Pretest information is therefore mandatory.