[Prenatal diagnosis of Fetal left-right asymmetry anomalies in a single-center cohort].

OBJECTIVE

To investigate the subtype distribution, clinical characteristics, and genetic causes in a single-center cohort of Fetal Left-right asymmetry anomalies (FLRAA).

METHODS

Seventy-nine typical FLRAA cases undergoing prenatal evaluation at Guangzhou Women and Children's Medical Center between January 1, 2011 and June 30, 2025 were included. Genetic analyses including karyotyping, copy number variation (CNV) detection, and gene sequencing were carried out, and genotype-phenotype correlation was explored. This study was approved by the Medical Ethics Committee of Guangzhou Women and Children's Medical Center (Ethics No.: 2015-112).

RESULTS

The cohort has included 43 cases of situs inversus totalis (54.4%), 8 cases of situs inversus incompletus/partialis (10.1%), 9 cases of heterotaxy-right isomerism/asplenia (11.4%), 10 cases of heterotaxy-left isomerism/polysplenia (12.7%), and 9 cases (11.4%) of undetermined subtypes prenatally. Among these, isolated FLRAA was observed in 28 cases (35.4%), while non-isolated FLRAA was identified in 51 cases. The non-isolated group included 26 cases (32.9%) with cardiovascular anomalies, 5 cases (6.3%) with extracardiac anomalies, and 20 cases (25.3%) with both cardiovascular and extracardiac anomalies. Genetic testing has revealed chromosomal abnormalities in 5 cases, pathogenic CNV in 1 case, and pathogenic/likely pathogenic monogenic variants in 4 cases. The identified variants involved multiple ciliary motility-related genes including DNAH11, DNAH9, and LRRC56.

CONCLUSION

FLRAA may exhibit diverse clinical manifestations and complex etiologies. This study has highlighted the value of integrated genetic testing and expanded the spectrum of pathogenic variants of key FLRAA-related genes. Above findings have provided critical insights for genetic counseling and pregnancy management. Further studies with larger cohorts and functional validation are warranted to elucidate the underlying pathogenic mechanisms.