Prenatal genetic diagnostics and postnatal outcomes of fetal auricular dysplasia

Auricular dysplasia is a common fetal anomaly. Despite existing studies in postnatal populations, there remains a paucity of prenatal data on genetic etiology and prognostic analysis for this condition. This study aimed to analyze the genetic etiology and associated postnatal outcomes of auricular dysplasia, in order to provide guidance for prenatal genetic counseling.

This retrospective cohort study evaluated 105 singleton and 5 twin pregnancies with prenatally diagnosed auricular dysplasia between May 2019 and June 2024. Genetic investigations included chromosomal microarray (CMA), copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) to elucidate potential genetic etiologies. Longitudinal postnatal follow-up was systematically conducted to assess auricular morphology, auditory function, and associated systemic anomalies, providing comprehensive prognostic insights.

Fetal auricular dysplasia predominantly manifests as unilateral involvement (with right-sided predominance), while bilateral cases are more frequently associated with concurrent multisystem developmental anomalies. Genetic analyses revealed trisomy 21 and CNVs of uncertain clinical significance, including 4q22.1 microdeletion, 3p12.2 microduplication, etc. In bilateral cases with multisystem anomalies, variants in SLC25A24, EFTUD2, and ABCA12 were identified. Postnatally, no pathogenic/likely pathogenic chromosomal or genetic variants were detected in isolated auricular dysplasia cases. However, in cases with concurrent systemic anomalies, compound heterozygous variants were identified in HSPA9 and ADGRV1. Follow-up data showed that 4 (12.90%) of prenatally diagnosed neonates exhibited no auricular malformations postnatally, and 12 (38.71%) had normal hearing, with auditory impairment mostly confined to the affected ear in unilateral cases.

Isolated auricular dysplasia is generally not associated with genetic abnormalities. However, bilateral auricular dysplasia with concurrent multisystem developmental anomalies demonstrates a correlation with pathogenic gene variants. Prenatal ultrasound diagnosis of auricular dysplasia carries a potential for misdiagnosis, but isolated cases typically manifest postnatally with auricular malformations and ipsilateral hearing impairment. In contrast, bilateral auricular dysplasia accompanied by multisystem anomalies may serve as a prognostic indicator of adverse fetal outcomes, necessitating comprehensive genetic and systemic evaluations.