Auriculocondylar syndrome (ACS) is an ultra-rare disorder that arises from developmental defects of the first and second pharyngeal arches. Three subtypes of ACS have been described so far, i.e., ACS1 (MIM: 602483), ACS2 (MIM: 600810), and ACS3 (MIM: 131240). The majority of patients, however, are affected by ACS2, which results from the mutations in the PLCB4 gene. Herein, we have described an 8-year-old male patient presenting with ACS2 and summarized the molecular and phenotypic spectrum of the syndrome. We have also compared the clinical features of our case to three other previously described cases (one sporadic and two familial) harboring the same heterozygous missense variant c.1862G>A, p.Arg621His in the PLCB4 gene. The mutation was detected using whole-exome sequencing (WES). Due to low coverage of WES and suspicion of somatic mosaicism, the variant was additionally reassessed by deep targeted next-generation sequencing panel of genes related to the craniofacial disorders, and next confirmed by Sanger sequencing. ACS2 presents high intra- and interfamilial phenotypic heterogeneity that impedes reaching an exact clinical and molecular diagnosis. Thus, describing additional cases, carrying even the known mutation, but resulting in variable phenotypes, is essential for better understanding of such orphan Mendelian diseases.

耳髁综合征 (ACS) 是一种极罕见的疾病，由第一和第二咽弓的发育缺陷引起。迄今为止，已描述了三种 ACS 亚型，即 ACS1 (MIM: 602483)、ACS2 (MIM: 600810) 和 ACS3 (MIM: 131240)。然而，大多数患者受到 ACS2 的影响，这是由PLCB4基因突变引起的。在此，我们描述了一名患有 ACS2 的 8 岁男性患者，并总结了该综合征的分子和表型谱。我们还将我们病例的临床特征与其他三个先前描述的病例（一个散发性和两个家族性）进行了比较，这些病例在 PLCB4 中具有相同的杂合错义变异 c.1862G>A，p.Arg621His基因。使用全外显子组测序（WES）检测突变。由于 WES 的低覆盖率和体细胞嵌合体的怀疑，该变异另外通过与颅面疾病相关的基因的深度靶向下一代测序面板重新评估，然后通过 Sanger 测序确认。ACS2 表现出高度的家族内和家族间表型异质性，阻碍了准确的临床和分子诊断。因此，描述其他病例，甚至携带已知突变，但导致可变表型，对于更好地了解此类孤儿孟德尔疾病至关重要。