Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature

Background: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457).

Methods: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2.

Results: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved.

Conclusion: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.