Predictor(s) of Abnormal Array Comparative Genomic Hybridization Results in Patients With Cleft Lip and/or Palate

Cleft lip and/or cleft palate (CL/P) occurs either as an isolated anomaly or as one manifestation of genetic syndromes. Chromosomal abnormalities from karyotype analysis are commonly seen in cases of nonisolated CL/P. This study was designed to evaluate the usefulness of clinical array comparative genomic hybridization (aCGH) testing in patients with CL/P. Our objectives were to identify the clinical phenotypes that are predicative of an abnormal aCGH result, correlate aCGH results with language outcome, and analyze the data in the abnormal aCGH results group.

Nonisolated CL/P patients who had clinical aCGH testing performed between 2009 and 2012 in the University of Alabama at Birmingham cytogenetics lab were enrolled. The demographic data, clinical phenotypes, and speech outcome were collected.

Two hundred forty-five nonisolated CL/P patients were studied, with 62 having an abnormal aCGH result compared to 183 patients with a normal aCGH result. The presence of developmental delay/intellectual disability (DD/ID), dysmorphic features, congenital anomalies, and/or family history of DD/ID were significantly higher in the abnormal aCGH group (P < .05). Neither the aCGH results nor the type of CL/P correlated with speech outcome. Finally, analysis of the abnormal aCGH result group revealed that DD/ID had a strong positive association with the copy number variation pathogenicity and the number of genes involved.

This study demonstrated the diagnostic value of clinical aCGH testing in CL/P patients who present with DD/ID, dysmorphic features, other congenital anomalies, and/or family history of DD/ID.