The Genetics of 241 Fetuses With Talipes Equinovarus: A 8-Year Monocentric Retrospective Study

This study aims to investigate the utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses diagnosed with talipes equinovarus (TE), as well as to explore the genetic factors contributing to TE.

The study reviewed a total of 241 fetuses with TE between January 2015 and December 2023, categorizing them into two groups based on the absence or presence of additional ultrasound anomalies: 163 cases (67.6%) in the isolated TE group and 78 cases (32.4%) in the syndromic TE group. Karyotyping and CMA were performed for all cases, with WES being performed for 18 cases that had normal karyotype and CMA results.

The results indicated a total detection rate of 16.2% (39/241) using karyotyping and CMA. Furthermore, the detection rates of karyotyping and CMA in the isolated TE group and syndromic TE group were 10.4% (17/163) and 28.2% (22/78) respectively, showing a statistically significant difference (p < 0.05). WES was conducted on 18 fetuses with normal karyotyping and CMA results. A total of six cases, consisting of five cases with pathogenic single nucleotide variant (SNV) and one case of variants of uncertain significance (VUS), were identified, resulting in a detection rate of 33.3% (6/18). The identified SNVs was associated with the RIT1, GNPNAT1, PEX1, RYR1, ASCC1, and GDAP1 genes. The detection rates of WES in the isolated TE group and syndromic TE group were 25% (1/4) and 35.7% (5/14) respectively, with no statistically significant difference (p > 0.05). The overall diagnostic yield of genetic testing was 18.7% (45/241) in fetuses with TE.

When prenatal ultrasound identifies fetal TE, chromosome karyotyping and CMA should be considered as the first-line diagnostic tests. Unlike previous studies, this study recommended WES in cases of normal CMA results for both isolated and syndromic fetal TE.