Risk assessment models in genetics clinic for array comparative genomic hybridization: Clinical information can be used to predict the likelihood of an abnormal result in patients

Article type: Research Article

Authors: Marano, Rachel M. | Mercurio, Laura | Kanter, Rebecca | Doyle, Richard | Abuelo, Dianne | Morrow, Eric M.^; | Shur, Natasha^;

Affiliations: Warren Alpert Medical School of Brown University, Providence, RI, USA | Division of Human Genetics, Rhode Island Hospital, Providence, RI, USA | Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Department of Family Medicine, Brown University, Providence, RI, USA | Department of Molecular Biology, Cell Biology and Biochemistry (MCB), Brown University, Providence, RI, USA

Note: [] Corresponding author: Natasha Shur, Division of Human Genetics, Rhode Island Hospital, 110 Lockwood St Ste 234, Providence, RI 02903, USA. Tel.: +1 401 444 8361; Fax: +1 401 444 3288; E-mail: nshur1@lifespan.org.

Abstract: Array comparative genomic hybridization (aCGH) testing can diagnose chromosomal microdeletions and duplications too small to be detected by conventional cytogenetic techniques. We need to consider which patients are more likely to receive a diagnosis from aCGH testing versus patients that have lower likelihood and may benefit from broader genome wide scanning. We retrospectively reviewed charts of a population of 200 patients, 117 boys and 83 girls, who underwent aCGH testing in Genetics Clinic at Rhode Island hospital between 1 January/2008 and 31 December 2010. Data collected included sex, age at initial clinical presentation, aCGH result, history of seizures, autism, dysmorphic features, global developmental delay/intellectual disability, hypotonia and failure to thrive. aCGH analysis revealed abnormal results in 34 (17%) and variants of unknown significance in 24 (12%). Patients with three or more clinical diagnoses had a 25.0% incidence of abnormal aCGH findings, while patients with two or fewer clinical diagnoses had a 12.5% incidence of abnormal aCGH findings. Currently, we provide families with a range of 10–30% of a diagnosis with aCGH testing. With increased clinical complexity, patients have an increased probability of having an abnormal aCGH result. With this, we can provide individualized risk estimates for each patient.

Keywords: aCGH testing, micro-array, medical management, genetic diagnosis, genetic testing

DOI: 10.3233/PGE-13044

Journal: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 25-32, 2013