Prenatal Diagnosis of Laterality Disorder Associated With NME7 Variants

Situs inversus totalis (SIT) is a rare congenital laterality disorder characterized by a mirror-image reversal of the thoracic and abdominal organs.Although isolated SIT is generally associated with a favorable prognosis, prenatal diagnosis requires careful evaluation to exclude associated structural malformations and syndromic presentations, as well as genetic investigation to identify a possible underlying etiology and improve prognostic assessment.The genetic basis of SIT is complex and remains incompletely understood.To date, genotype-phenotype correlations for SIT-associated genetic variants remain poorly established.We report the prenatal and postnatal clinical course of a fetus with isolated SIT carrying a homozygous intragenic deletion of the NME7 gene, identified by whole-exome sequencing.A primigravida woman was referred at 22 + 2 weeks of gestation after dextrocardia was identified during the second-trimester morphology scan.Detailed ultrasound and fetal echocardiography were performed to assess organ laterality and exclude associated structural abnormalities.An invasive diagnostic procedure (amniocentesis) was performed, including chromosomal microarray analysis (CMA) and trio whole-exome sequencing.Ultrasound confirmed isolated SIT, characterized by dextrocardia, a right-sided stomach, and a left-sided liver and gallbladder.Echocardiography revealed normal cardiac anatomy and function.CMA identified a maternally inherited Xp22.33 deletion encompassing the entire SHOX gene, which was detected in the mother but not in the father and was considered an incidental finding.Trio whole-exome sequencing identified a homozygous, likely pathogenic intragenic deletion involving exons 2-7 of the NME7 gene.Targeted parental DNA analysis confirmed that both parents were heterozygous carriers of the deletion.The pregnancy was continued based on the present molecular findings, since the implication of NME7 variants seemed to be responsible for a non-syndromic form of SIT.A healthy female infant was delivered at term.Postnatal evaluation confirmed SIT with a small atrial septal defect with no hemodynamic impact and no other associated anomalies.This case highlights the additional diagnostic value of whole-exome sequencing in fetuses with apparently isolated laterality abnormalities.It adds to the currently limited evidence linking NME7 variants to isolated SIT.This case also emphasizes the importance of multidisciplinary assessment and genetic counseling to optimize diagnosis, prognostic evaluation, parental counseling, and postnatal management.