Prenatal diagnosis of cleft lip and palate: a study of clinical utility

Abstract Background When a fetus was found has cleft lip palate (CL/P) by prenatal anatomical ultrasound assessment, it is difficult to determine the CL/P is isolated or companied with other animalities such as intellectual disability. We preformed comprehensive genetic test to support prenatal genetic counselling for CL/P fetus which is detected by ultrasound screening. Results 105 unrelated fetuses with CL/P were enrolled. After excluding aneuploidy cases, SNP array and clinical exome sequencing (CES) were preformed simultaneously. All the fetuses were followed-up. Fetuses with CL/P were divided into two groups, cleft lip (CL)and cleft palate with or without cleft lip (CP/CLP). The detection rate was 12.4% (13/105) of the cases, in which SNP array contributed 3.8% (4/105) while CES added 8.6% yields. The positive rate of the CL group was lower than that of the CP/CLP group (0% (0/23) versus 15.9% (13/82), P = 0.067). CP/CLP with additional anomalies has higher positive rate than that of the apparently isolated CP/CLP (53.3% (8/15) versus 7.5% (5/67), P < 0.001). Furthermore, midline or bilateral CP/CLP had different yields in subgroups of CP/CLP. The rate of termination of pregnancy in positive group is much higher than that of the negative group (84.6% (11/13) versus 36.9% (31/84)). Conclusions Prenatal diagnosis with SNP array companied with CES was helpful for etiology analysis of fetuses with CL/P. Genetic etiology analysis was more valuable for CP/CLP than for CL. Moreover, SNP array companied with CES could change the clinical outcome for prenatal CL/P fetuses and reduce the residual risk for negative cases.