Biallelic truncating variants in VGLL2 cause syngnathia in humans.

BACKGROUND: Syngnathia is an ultrarare craniofacial malformation characterised by an inability to open the mouth due to congenital fusion of the upper and lower jaws. The genetic causes of isolated bony syngnathia are unknown. METHODS: We used whole exome and Sanger sequencing and microsatellite analysis in six patients (from four families) presenting with syngnathia. We used CRISPR/Cas9 genome editing to generate vgll2a and vgll4l germline mutant zebrafish, and performed craniofacial cartilage analysis in homozygous mutants. RESULTS: We identified homozygous truncating variants in vestigial-like family member 2 (VGLL2) in all six patients. Two alleles were identified: one in families of Turkish origin and the other in families of Moroccan origin, suggesting a founder effect for each. A shared haplotype was confirmed for the Turkish patients. The VGLL family of genes encode cofactors of TEAD transcriptional regulators. Vgll2 is regionally expressed in the pharyngeal arches of model vertebrate embryos, and morpholino-based knockdown of vgll2a in zebrafish has been reported to cause defects in development of pharyngeal arch cartilages. However, we did not observe craniofacial anomalies in vgll2a or vgll4l homozygous mutant zebrafish nor in fish with double knockout of vgll2a and vgll4l. In Vgll2 -/- mice, which are known to present a skeletal muscle phenotype, we did not identify defects of the craniofacial skeleton. CONCLUSION: Our results suggest that although loss of VGLL2 leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development.

Diagnostic reliability of 3.0-T MRI for detecting osseous abnormalities of the temporomandibular joint.

We compared the diagnostic reliability of 3.0-T magnetic resonance imaging (MRI) for detection of osseous abnormalities of the temporomandibular joint (TMJ) with that of the gold standard, cone-beam computed tomography (CBCT). Fifty-six TMJs were imaged with CBCT and MRI, and images of condyles and fossae were independently assessed for the presence of osseous abnormalities. The accuracy, sensitivity, and specificity of 3.0-T MRI were 0.88, 1.0, and 0.73, respectively, in condyle evaluation and 0.91, 0.75, and 0.95 in fossa evaluation. The McNemar test showed no significant difference (P > 0.05) between MRI and CBCT in the evaluation of osseous abnormalities in condyles and fossae. The present results indicate that 3.0-T MRI is equal to CBCT in the diagnostic evaluation of osseous abnormalities of the mandibular condyle.

An image-guided technique for puncture of the superior temporomandibular joint cavity: clinical comparison with the conventional puncture technique.

OBJECTIVE: The objective of this study was to compare an image-guided puncture technique (IGPT) with conventional puncture technique (CPT) with respect to accuracy of needle entry, maximal mouth opening, and pain in pumping manipulation treatment of internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: The subjects comprised 178 patients with internal derangement of the TMJ with closed lock. Treatment was provided using CPT in 102 cases and IGPT in 76 cases. Three variables, number of repunctures, maximal mouth opening distance, and pain threshold according to a visual analogue scale, were measured and compared between IGPT and CPT groups. RESULTS: Access to the superior joint cavity was achieved without correcting the puncture point in 97% of patients who underwent IGPT and 82% of patients in the CPT group. Significant differences were seen in 1-week maximal mouth opening and pain threshold between IGPT and CPT groups (P < .05 each) and resetting of the puncture point was significantly less frequent using IGPT compared with CPT (P < .05). CONCLUSIONS: IGPT is effective for pain mitigation and improves mouth opening during the early postoperative period after pumping manipulation treatment.