A familial PLCB4 mutation causing auriculocondylar syndrome 2 with variable severity.

Auriculocondylar syndrome (ARCND, MIM #614669, #602483, and #615706); also known as ''question-mark ear syndrome'' or ''dysgnathia complex'', is a rare craniofacial malformation of first and second branchial arches with a prevalence of <1/1,000,000. It is characterized by a distinctive auricular malformation (question mark ear (QME)) and highly variable mandibular anomalies. Variants found in PLCB4, GNAI3, and in EDN1 genes are responsible for >90% of tested ARCND patients. Whole exome sequencing in a multigenerational Egyptian kindred with high intrafamilial variability revealed a known heterozygous missense variant in PLCB4 (NM_000933.3:c.1862G>A:p.(Arg621His)). This report increases the number of molecularly characterized ARCND patients to 29 and emphasizes the highly variable clinical presentation within families.