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. 2024 Aug 21;50(1):152.
doi: 10.1186/s13052-024-01720-y.

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

Shujuan Yan  1 , Qiuxia Yu  1 , Hang Zhou  1 , Ruibin Huang  1 , You Wang  1 , Chunling Ma  1 , Fei Guo  1 , Fang Fu  1 , Ru Li  1 , Fucheng Li  1 , Xiangyi Jin  1 , Li Zhen  1 , Min Pan  1 , Dongzhi Li  1 , Can Liao  2
Affiliations

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

Shujuan Yan et al. Ital J Pediatr. .

Abstract

Backgroud: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes.

Methods: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes.

Results: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed.

Conclusions: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P.

Keywords: Chromosomal microarray analysis; Cleft lip and palate; Genetic counseling; Prenatal diagnosis.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flowchart of genetic analysis progression in cohort of fetuses with CL/P
Fig. 2
Fig. 2
Analysis of the detection of clinically significant variants among different subgroups in singleton pregnancies affected by CL/P. A The number of cases with non-isolated and isolated CL/P ultrasound abnormalities that underwent CMA. B Comparison of CMA detection rate of isolated and non-isolated CL/P in fetuses of singleton and twin pregnancies; (C) Comparison of CMA detection rate of CL, CP and CLP in fetuses with isolated and non-isolated CL/P. * p > 0.05; # p < 0.05; ##p < 0.001
See this image and copyright information in PMC

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