Auriculo‐condylar syndrome. Confronting a diagnostic challenge

Abstract

Auriculo-condylar syndrome (ACS) is characterized by typical ears malformation (so-called "question mark" ears), prominent cheeks, microstomia, and abnormality of the temporomandibular joint and condyle of the mandible. In this report we describe a new simplex case and a previously unreported family with affected individuals in three generations documenting clinical variability. Linkage study for markers located in candidate region for ACS1 (1p21.1-q23.3) was excluded in our familial case, reinforcing the hypothesis of genetic heterogeneity for this condition. A review of the literature focusing diagnostic criteria and features of ACS was performed.

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome

“…Other features of variable frequency include prominent cheeks, microstomia, palatal anomalies, glossoptosis, pre- and postauricular tags, facial asymmetry, crowded teeth and hearing loss (HL) (reviewed in Kokitsu–Nakata et al 1). QME can occur as an isolated anomaly (IQME; MIM 612798).…”

Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect

“…1 We previously mapped the first ACS locus to 1p21.1-q23.3 (ACS1) 2 in a large Brazilian family that was initially described by GuionAlmeida et al 3 Genetic heterogeneity was also suggested as affected members of two other families were not associated with this locus. 2,4 Rieder et al 5 subsequently showed that variants in phospholipase C beta 4 (PLCB4), at 20p12.2, and in guanine nucleotide binding protein (G protein) alpha-inhibiting activity polypeptide 3 (GNAI3), located within the 1p21.1-q23.3 candidate interval, are responsible for most ACS cases. GNAI3 and PLCB4 are predicted to be signaling molecules of the endothelin 1 (EDN1)-endothelin receptor type A (EDNRA) pathway, which is important for patterning of the pharyngeal arches in animal models.…”

Understanding the basis of auriculocondylar syndrome: Insights from human, mouse and zebrafish genetic studies

“…It is an apparently rare condition whose prevalence is still unknown. The first report appeared in 1978 [Uuspaa, 1978], which was followed by reports of several other isolated cases and a few familial cases [Baker et al, 2004; Divizia et al, 2002; Erlich et al, 2000; Gerkes et al, 2008; Gordon et al, 2013; Greig et al, 2012; Guion-Almeida et al, 1999; Guion-Almeida et al, 2002; Jampol et al, 1998; Kokitsu-Nakata et al, 2011; Masotti et al, 2008; Ozturk et al, 2005; Priolo et al, 2000; Propst et al, 2013; Rieder et al, 2012; Storm et al, 2005; Stuffken and Tuinzing, 2008]. Vertical disease segregation through several generations in a few families suggested an autosomal dominant pattern of inheritance for ACS [Guion-Almeida et al, 2002; Jampol et al, 1998; Masotti et al, 2008; Storm et al, 2005].…”

“…The severity of the malformation varies and can range from a minor indentation to complete clefting between the lobe and helix (Figure 1). Other features of variable frequency include microstomia, full cheeks, palatal anomalies, glossoptosis, crowded teeth, facial asymmetry, postauricular tags and hearing loss (Table I) [Gordon et al, 2013; Kokitsu-Nakata et al, 2011]. Among ACS patients, there is a high degree of inter- and intra-familial phenotypic variation, including non-penetrance [Gordon et al, 2013; Ozturk et al, 2005; Rieder et al, 2012].…”

“…It is an apparently rare condition whose prevalence is still unknown. The first report appeared in 1978 [Uuspaa, 1978], which was followed by reports of several other isolated cases and a few familial cases [Jampol et al, 1998;Guion-Almeida et al, 1999Erlich et al, 2000;Priolo et al, 2000;Divizia et al, 2002;Baker et al, 2004;Ozturk et al, 2005;Storm et al, 2005;Gerkes et al, 2008;Masotti et al, 2008;Stuffken and Tuinzing, 2008;Kokitsu-Nakata et al, 2011;Greig et al, 2012;Rieder et al, 2012;Gordon et al, 2013;Propst et al, 2013]. Vertical disease segregation through several generations in a few families suggested an autosomal dominant pattern of inheritance for ACS [Jampol et al, 1998;Guion-Almeida et al, 2002;Storm et al, 2005;Masotti et al, 2008].…”