Syndromes of the first and second pharyngeal arches: A review

Abstract

Our aim in this review is to discuss currently known mechanisms associated with three important syndromes of the first and second pharyngeal arches: Treacher Collins syndrome (TCS), Oculo-auriculo-vertebral syndrome (AOVS) and Auriculo-Condylar syndrome (ACS) or question mark ear syndrome. TCS and ACS are autosomal dominant diseases, with nearly complete penetrance and wide spectrum of clinical variability. The phenotype of the latter has several overlapping features with OAVS, but OAVS may exist in both sporadic and autosomal dominant forms. Mutations in the TCOF1 gene are predicted to cause premature termination codons, leading to haploinsuficiency of the protein treacle and causing TCS. Low amount of treacle leads ultimately to a reduction in the number of cranial neural crest cells migrating to the first and second pharyngeal arches. Other than TCS, the genes associated with ACS and OAVS are still unknown. The first locus for ACS was mapped by our group to 1p21-23 but there is genetic heretogeneity. Genetic heterogeneity is also present in OAVS. Based on the molecular analysis of balanced translocation in an OAVS patient, it has been suggested that abnormal expression of BAPX1 possibly due to epigenetic disregulation might be involved with the etiology of OAVS. Involvement of environmental events has also been linked to the causation of OAVS. Identification of factors leading to these disorders are important for a comprehensive delineation of the molecular pathways underlying the craniofacial development from the first and the second pharyngeal arches, for genetic counseling and to open alternative strategies for patient treatment.

Syndromes of the First and Second Branchial Arches, Part 1: Embryology and Characteristic Defects

“…Other changes are related to deregulation of cell-signaling pathways triggered by a combination of genetic and environmental factors. 2 The manifestation and severity of the congenital abnormality depend on the alteration of gene-expression profiles. 2,3 The pluripotent nature of synchronously migrating cells is thought to, at least partially, explain the appearance and pattern of mesenchymal and epithelial abnormalities seen with syndromic defects of the BAs.…”

“…2 The manifestation and severity of the congenital abnormality depend on the alteration of gene-expression profiles. 2,3 The pluripotent nature of synchronously migrating cells is thought to, at least partially, explain the appearance and pattern of mesenchymal and epithelial abnormalities seen with syndromic defects of the BAs. Multiple craniofacial syndromes have been shown to result from an abnormality in the quantity or quality of neural crest cell migration (ie, TCS and VCFS).…”

Syndromes of the First and Second Branchial Arches, Part 2: Syndromes

“…Inter-and intrafamilial variability is marked, and some obligate carriers are nonpenetrant. [24][25][26] A genome-wide search of 2 families with ACS revealed evidence of linkage to 1p21.1-q23.3 in 1 of the families and nonlinkage in the other. These findings suggest evidence for genetic heterogeneity and the existence of at least 2 loci responsible for this syndrome.…”

“…Limb anomalies do not occur in TCS, which helps differentiate it from other syndromes that manifest with similar facial features. 24,[35][36][37][38] Facial deformaties are prioritized and addressed based on function and the basis for proper development. Surgical techniques have been described to address most of the anomalous development in TCS.…”

Auriculo-condylar syndrome

“…[4][5][6] The typical clinical appearance of the syndrome includes prominent and constricted ears, stenosis of the ear canals, hypoplastic condyles of the mandible, temporomandibular joint abnormalities, microstomia, malocclusion, puffy cheeks, and a round face. 4,[6][7][8] However, because of high clinical variability, other signs can be present, including a simple external auricular malformation, 9 cleft palate, hypoplastic tongue, glossoptosis, hypotonia, facial asymmetry, respiratory distress, and apnea. 5,10,11 Vincent et al 12 in 1961 and Divizia et al 13 in 2002 reported cases with ear malformations associated with urogenital abnormalities.…”