Prenatal Diagnosis and Pregnancy Outcomes of Fetuses With Orofacial Cleft: A Retrospective Cohort Study in Two Centres in Hong Kong

Abstract

Objective To evaluate the local incidence of orofacial cleft (OFC) encountered in fetal morphology scan and prenatal diagnosis, genetic etiology of fetuses with or without other structural abnormalities, and their pregnancy outcomes. Design Retrospective cohort study. Setting Two maternal fetal medicine units, tertiary hospitals, Hong Kong. Participants All pregnant women with antenatal diagnosis of fetal OFC between January 2016 and December 2020 (N = 66). Results OFC has an incidence of 0.13% among pregnancies in Hong Kong and 28.8% (19/66) were syndromic cleft that exhibited other fetal structural anomalies. There were 55 cases (84.6%) who opted for invasive prenatal diagnostic testing. Genetic defects were identified in 25.8% (17/66) of this cohort, including 14 pathogenic variants. The detection rate in the syndromic cases is 68.4% (13/19) which was significantly higher than 8.5% (4/47) among non-syndromic cases. Aneuploidies would be the most common cause, accounting for 9.1% (6/66). Chromosomal microarray analysis (CMA) provided an incremental diagnostic yield of 6.1% compared to conventional karyotyping. A total of 29 live births including 3 cases of a variant of uncertain significance and 26 cases without genetic abnormalities detected have continued pregnancy to birth. There were 87.5% (21/24) without detectable pathogenic genetic abnormality reported good long-term outcomes. The chance of OFC fetuses having a good long-term outcome was significantly higher if no genomic variant was detected ( P < .001). Conclusions Invasive prenatal tests with CMA should be offered to pregnancies with OFC regardless of the type. It has provided incremental diagnostic yield over conventional karyotyping and helped in prenatal and genetic counseling. A negative result in non-syndromic OFC favors couples to keep the pregnancy.

Association of prenatal Cleft Lip and Palate ultrasound abnormalities with copy number variants at a single Chinese tertiary center

“…These syndromic defects are attributed to mutations and deletions that lead to the loss of function of one or more genes 18 . In our cohort, there was a signi cant difference in the detection rate of isolated CL/CP and nonisolated CL/CP (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001), a nding which is similar to previous studies 11 .…”

“…According to report that CMA identi ed clinically signi cant genomic alterations in approximately 6% of fetuses exhibiting abnormal ultrasound and with normal karyotype 9 . While there have been several research publications on prenatal diagnosis of fetal CL/CP utilizing CMA 10,11 , the comprehensive assessment of the speci c information about fetuses with CL/CP through CMA is currently limited.…”

Exome sequencing improves genetic diagnosis of congenital orofacial clefts

“…Burnell et al reported a live birth rate of 84.5% (82/97) and 84.4% (65/77) long-term favorable outcomes without complex disorders in isolated CL/P cases. Li et al found a live birth rate of 43.9% (29/66) and 87.5% (21/24) had good long-term outcomes without any detectable pathogenic genetic abnormalities ( Burnell et al, 2014 ; Li et al, 2022 ). In our study, the live birth rate was 48.6% (52/107), similar to Li’s study.…”