Craniofacial Cephalometric Morphology in Polish Adolescents with Cleft Palate Only.

Background: Cephalometric studies indicate that craniofacial morphology in patients with cleft palate only (CPO) differs from other forms of orofacial clefts and healthy patients. Planning orthodontic treatment for patients with different craniofacial deformities requires knowledge on the craniofacial complex. The aim of the present study was to describe the cephalometric craniofacial morphology in adolescents with cleft palate only compared to generally healthy orthodontic patients. Methods: The study comprised 100 lateral cephalograms (taken in the years 2003-2020) of Polish patients with cleft palate only aged from 11.1 to 14.2 (mean age 12.43 y) and a matched control group of 100 children without orofacial clefts aged 12-14 (mean age 12.25). All digital images were analyzed in specialized cephalometric software. Results: Statistically significantly lower values of both SNA (p < 0.001) and ANB (p < 0.001) were found in the study group versus the control group. Mandibular line to cranial base angle (ML-NSL) as well as maxillary base to cranial base (NL-NSL) were significantly higher in the CPO group. Both the maxilla and mandible were rotated distally in CPO. Moreover, the intermaxillary vertical angle (ML-NL) was reduced in CPO. Mandibular angle in CPO was significantly higher (p = 0.005), reflecting posterior mandibular rotation. Conclusions: In adolescents with CPO, maxillary deficiency is found, without a severe sagittal jaw discrepancy, with a slight compensatory lingual inclination of the lower incisors. Mandibular deficiency in CPO is concurrent with posterior rotation and an increased mandibular angle.

Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.

A Rare Case of Fibrous Dysplasia Presenting With Facial Swelling and Craniofacial Deformity in a 13-Year-Old Girl.

Fibrous dysplasia (FD) is a rare benign skeletal disorder that replaces normal bone with fibrous tissue and immature woven bone. We present a case of a 13-year-old girl with right-sided facial swelling and craniofacial deformity since birth, accompanied by nasal obstruction and difficulty in breathing and swallowing. Computed tomography (CT) imaging revealed an expansile bony lesion with a ground-glass matrix involving multiple craniofacial bones. Histopathological examination confirmed the diagnosis of FD. Management involved regular monitoring and conservative measures, with surgical intervention reserved for symptomatic progression or cosmetic concerns. This case underscores the importance of considering FD in the differential diagnosis of craniofacial asymmetry and highlights the collaborative approach to patient care. Further research is needed to optimize management strategies and outcomes for pediatric patients with FD.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

A Case of Trigeminal Neuralgia in an Adult Patient With Lambdoid Synostosis.

Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.