Auriculocondylar syndrome-1 (ARCND1) is an autosomal dominant disorder of the first and second pharyngeal arches and is characterized by malformed ears (question mark ears), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia (summary by Masotti et al., 2008).
Genetic Heterogeneity of Auriculocondylar Syndrome
See also ARCND2A (614669), caused by heterozygous mutation in the PLCB4 gene (600810) on chromosome 20p12.3-p12.2; ARCND2B (620458), caused by biallelic mutation in the PLCB4 gene; ARCND3 (615706), caused by mutation in the EDN1 gene (131240) on chromosome 6p24; and ARCND4 (620457), caused by mutation the HDAC9 gene (606543) on chromosome 7p21.
See also 612798 for isolated question mark ears.
Reviews
Kokitsu-Nakata et al. (2012) tabulated clinical findings in 24 reported cases of auriculocondylar syndrome. The most common clinical signs observed were ear constriction (100%), abnormal temporomandibular joint (100%), mandibular condyle abnormality (93%), malocclusion (93%), round face (78%), microstomia (78%), micrognathia (78%), prominent cheeks (74%), hearing loss (56%), abnormal palate (55%), and crowded teeth (50%). The authors noted that the phenotype was highly variable in severity, even within families.
Liu et al. (2021) reviewed 19 published cases of ARCND1 and tabulated the common features, including micrognathia (79%), auricular malformation (68%), microstomia (67%), prominent cheeks (63%), mandibular hypoplasia (58%), and round face (58%). Asymmetry of mandibular and auricular malformations was present in 4 patients, and the lesions were either more severe on the right or only the right side was affected, suggesting a predilection for right-sided deformities. The authors also noted that severe cases mostly occurred in female patients. Prenatal findings were available in 3 patients, and all showed polyhydramnios, with 2 having micrognathia evident on ultrasonography. The authors suggested that severe micrognathia and mandibular hypoplasia accompanied by polyhydramnios might be prenatal indicators of ARCND.
Using a standardized questionnaire sent to referring physicians, Vegas et al. (2022) collected clinical data on 39 patients from 27 families with auriculocondylar syndrome and mutation in the GNAI3, PLCB4, or EDN1 genes. PLCB4 was the most common gene associated with ARCND, being mutated in 16 (59%) of the 27 families. Incomplete penetrance and/or variable expression was observed within families. [from
OMIM]