クルーゾン症候群

This case report describes a successful oral-to-nasal endotracheal tube exchange using a combined video laryngoscopy and fiberoptic bronchoscopy (FOB) technique in a 48-year-old patient with Crouzon syndrome following modified Le Fort III osteotomy and Le Fort I osteotomy. Severe midfacial disruption, bleeding, and secretions precluded the use of FOB alone. The video laryngoscope provided a continuous glottic view and enabled suctioning, while guiding the FOB into the trachea alongside the existing tube. The exchange was completed smoothly within 5 minutes without desaturation. This hybrid approach is an effective strategy for managing difficult airway exchange in complex maxillofacial surgery.

Crouzon syndrome is a syndromic craniosynostosis characterized by premature fusion of cranial sutures and variability in cranial phenotype, which is poorly explained by classical growth rules such as Virchow's law. This study tested whether quantitative, continuous assessment of calvarial suture patency can help explain endocranial shape variability when categorical suture descriptions fail. We retrospectively analyzed preoperative cranial CT scans from children with FGFR2-related bicoronal craniosynostosis and age-matched controls (birth to 4 years). Endocasts were reconstructed using a semiautomated pipeline and analyzed with three-dimensional geometric morphometrics. Suture patency of major calvarial sutures was quantified as a continuous measure and converted into age-adjusted residuals, allowing deviations from control closure dynamics to be assessed independently of age. Intracranial volume increased with age at comparable rates in both groups, indicating preserved global endocranial growth. However, endocranial shape and its allometric relationship to growth differed between groups. While age-adjusted suture patency showed only weak associations with shape in controls, suture residuals covaried strongly with coherent, system-level endocast shape changes in Crouzon patients, including alterations in anteroposterior proportions and cranial fossa configuration. Morphological clusters did not map one-to-one onto suture closure patterns, indicating nonlocal and context-dependent effects. These findings suggest that suture-based models such as Virchow's law fail to predict cranial shape in syndromic craniosynostosis. By treating suture patency as a continuous, age-adjusted variable embedded within a coupled brain-skull growth system, this study suggests that Crouzon syndrome could act as a test case for quantitative, system-level models of craniofacial development.

BACKGROUND: Treacher Collins syndrome (TCS) is a congenital craniofacial disorder characterized by malar and mandibular hypoplasia, downward-slanting palpebral fissures, and conductive hearing loss. Pathogenic variants in TCOF1 account for most cases, with POLR1D, POLR1C, and POLR1B also implicated. METHODS: Whole-exome sequencing was performed in a two-generation Chinese family with TCS, followed by Sanger sequencing validation. Clinical features were systematically evaluated, and bioinformatic analyses combined with structural modeling were employed to assess the potential pathogenicity of the identified variant. RESULTS: In this study, a novel heterozygous frameshift variant in TCOF1 (NM_001371623.1:c.1601_1602delCC, p.Pro534Leufs*15) was identified in the proband and his affected father. The proband presented classic TCS features including craniofacial skeletal hypoplasia, downward-slanting palpebral fissures, and conductive hearing loss. He also carried a right-sided preauricular fistula, a nonclassical feature of TCS. The same variant was detected in his affected father with a substantially milder phenotype, indicating marked intrafamilial phenotypic variability. Bioinformatic analysis and structural modeling predicted that this variant produces a severely truncated Treacle protein lacking key functional domains, which is predicted to disrupt nucleolar localization and ribosome biogenesis. CONCLUSION: Our findings expand the variant spectrum of TCOF1, highlight phenotypic heterogeneity in TCS, and reinforce the critical role of molecular diagnosis in distinguishing TCS from phenotypically overlapping craniofacial syndromes.

BACKGROUND: Crouzon's syndrome is a rare autosomal dominant craniosynostosis disorder characterized by midfacial hypoplasia due to premature fusion of the coronal and sagittal sutures. Facial features are typical in the form of a hypoplastic maxilla, shallow orbits, and mandibular prognathism. The condition is usually diagnosed during infancy or early childhood because of characteristic craniofacial features. Delayed diagnosis during adolescence is uncommon, and severe infective complications as the initial presentation are exceedingly rare. CASE SUMMARY: A 14-year-old boy with no known craniofacial diagnosis presented to the emergency department with fever, headache, altered mentation, and left eye swelling. Examination revealed proptosis, chemosis, and purulent discharge from the left eye, along with midfacial hypoplasia and shallow orbits. Computed tomography and magnetic resonance imaging demonstrated extensive pansinusitis, orbital cellulitis, frontal bone osteomyelitis, and craniosynostosis-related craniofacial abnormalities. Initial empirical antimicrobial therapy was started and subsequently escalated following the isolation of carbapenem-resistant Pseudomonas aeruginosa. Owing to progressive disease, urgent functional endoscopic sinus surgery (FESS) was performed. The patient demonstrated rapid clinical improvement with resolution of orbital swelling and recovery of neurological status. Subsequent genetic testing confirmed an FGFR2 mutation, establishing the diagnosis of Crouzon syndrome. CONCLUSION: This case highlights a rare late presentation of previously undiagnosed Crouzon syndrome with life-threatening infective complications. Recognition of craniofacial dysmorphism in patients presenting with severe sinonasal infections is essential for timely diagnosis and multidisciplinary management. Culture-directed antimicrobial therapy combined with appropriately planned FESS can result in excellent clinical outcomes.

Introduction We investigated two siblings from a consanguineous Kurdish family presenting with a specific facial phenotype (prominent forehead, supraorbital ridges, broad nose, depressed nasal bridge), severe short stature with biochemical features of growth hormone (GH) deficiency, microcephaly, and developmental delay. Whole-exome sequencing identified a homozygous variant (c.3119G>A, p.Arg1040His) in gene ZSWIM6, a putative transcription factor. Previously, only de novo heterozygous ZSWIM6 variants were known, causing either acromelic frontonasal dysostosis (AFND) or severe intellectual disability without craniofacial or skeletal anomalies. We aimed to characterize the functional impact of these three distinct variants to understand the resulting genotype-phenotype correlations. Methods The three ZSWIM6 variants were prepared in vitro by site-directed mutagenesis. Transcriptional activity was assessed in HEK293 cells using dual-luciferase reporter assays for HECW2 and ZIC2 promoters, previously hypothesized to possess functional links to ZSWIM6. In addition, in silico 3D structural modelling was performed using AlphaFold to predict the impact of each mutation on protein conformation and surface charge. Results The siblings shared partial overlap with prior ZSWIM6-associated phenotypes but also exhibited a distinct clinical presentation. Functional assays confirmed ZSWIM6 is a transcriptional regulator of the HECW2 and ZIC2 promoters. The three variants showed different effects on transcriptional regulation: the p.Arg1040His variant reduced ZIC2 activation (loss-of-function), p.Arg1163Trp enhanced ZIC2 activation (gain-of-function), and p.Arg913Ter specifically increased HECW2 activation (derepression). The 3D structural modelling predicted that p.Arg1040His and p.Arg1163Trp alter local surface charge without disrupting the overall fold, while p.Arg913Ter truncates ZSWIM6, potentially affecting the DNA binding interactions. Conclusion We report the first-ever homozygous ZSWIM6 variant, causing a novel phenotype of severe syndromic short stature with biochemical features consistent with GH deficiency and developmental delay. Our findings demonstrate that ZSWIM6 is a key transcriptional regulator and that allele-specific disturbances drive the marked clinical heterogeneity of ZSWIM6-related disorders.