Prenatal genetic findings using karyotyping and chromosomal microarray analysis in the first-occurrence typical...

Orofacial clefts (OFCs), including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are among the most common congenital anomalies. Prenatal genetic evaluation plays a critical role in guiding pregnancy management. This study aimed to evaluate genetic findings and pregnancy outcomes in first-occurrence fetal OFCs using conventional karyotyping and SNP array analysis.

We retrospectively reviewed 205 pregnancies diagnosed with first-occurrence OFCs between December 2010 and December 2024. Cases were categorized as non-syndromic or syndromic OFCs based on the presence of additional malformations. All cases underwent conventional karyotyping; 138 also underwent SNP array analysis. Pregnancy outcomes were obtained through medical records and follow-up.

Of the 205 cases, 74.6% were classified as non-syndromic OFCs and 25.4% were syndromic OFCs. Chromosomal abnormalities were detected in 11.7% of all OFCs, all occurring within the syndromic group, representing 46.2% of syndromic cases. The most frequent abnormalities were trisomy 13 and trisomy 18. SNP array analysis detected additional four clinically significant CNVs, improving diagnostic yield, particularly in syndromic OFCs. The termination rate was significantly higher in syndromic OFCs (90.2%) compared to non-syndromic cases (25.5%). Follow-up data on subsequent pregnancies were obtained for 45 cases, and no recurrent OFCs were observed.

Most cases of first-occurrence OFCs are isolated and carry a low risk of chromosomal abnormalities. Genetic evaluation is particularly valuable in syndromic OFCs, where the likelihood of clinically significant chromosomal abnormalities is higher. The combined use of karyotyping and SNP array analysis enhances diagnostic accuracy and provides important guidance for pregnancy management.