p53 inhibitor or antioxidants reduce the severity of ethmoid plate deformities in zebrafish Type 3 Treacher Collins syndrome model.

Treacher Collins syndrome-3 (TCS-3) is a rare congenital craniofacial disorder attributed to variants in the RNA pol I subunit C (POLR1C). The pathogenesis of TCS-3 linked to polr1c involves the activation of apoptosis-dependent p53 pathways within neural crest cells (NCCs). This occurs due to disruptions in ribosome biogenesis, and the restoration of polr1c expression in early embryogenesis effectively rescues the observed craniofacial phenotype in polr1c-deficient zebrafish. Clinical variability in TCS patients suggests interactions between genes and factors like oxidative stress. Elevated production of reactive oxygen species (ROS) in epithelial cells may worsen phenotypic outcomes in TCS individuals. Our study confirmed excessive ROS production in facial regions, inducing apoptosis and altering p53 pathways. Deregulated cell-cycle and epithelial-to-mesenchymal transition (EMT) genes were also detected in the TCS-3 model. Utilizing p53 inhibitor (Pifithrin-α; PFT-α) or antioxidants (Glutathione; GSH and N-Acetyl-L-cysteine; NAC) effectively corrected migrated NCC distribution in the pharyngeal arch (PA), suppressed oxidative stress, prevented cell death, and modulated EMT inducers. Crucially, inhibiting p53 activation or applying antioxidants within a specific time window, notably within 30 h post-fertilization (hpf), successfully reversed phenotypic effects induced by polr1c MO.

Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: Report of a new family and review of the literature.

Treacher Collins syndrome (TCS) is a frequent cause of mandibulofacial dysostosis. To date, TCS-causing mutations in three genes, namely TCOF1, POLR1D, and POLR1C have been identified. TCS is usually inherited in an autosomal dominant manner, with a high clinical variability and no phenotype-genotype correlation. Up-to now, five families have been reported with an autosomal recessive mode of inheritance due to mutations in POLR1D or POLR1C. We report here a new family with two sisters affected by mild TCS carrying compound POLR1C heterozygous mutations, and review the literature on mild forms of TCS, autosomal recessive inheritance in this syndrome and POLR1C mutations.

Treacher Collins syndrome: New insights from animal models.

Treacher Collins syndrome (TCS, OMIM: 154500), an autosomal-dominant craniofacial developmental syndrome that occurs in 1 out of every 50,000 live births, is characterized by craniofacial malformation. Mutations in TCOF1, POLR1C, or POLR1D have been identified in affected individuals. In addition to established mouse models, zebrafish models have recently emerged as an valuable method to study facial disease. In this report, we summarized the two updated articles working on the pathogenesis of the newly identified polr1c and polr1d TCS mutations (Lau et al., 2016; Noack Watt et al., 2016) and discussed the possibility of using the anti-oxidants to prevent or rescue the TCS facial phenotype (Sakai et al., 2016). Taken together, this article provides an update on the disease from basic information to pathogenesis, and further summarizes the suggested therapies from recent laboratory research.

Treacher Collins syndrome: an undescribed characteristic of the condition and its management with botulinum toxin and surgery.

Mandibulofacial dysostosis (Treacher Collins syndrome) is associated with clinical abnormalities of structures derived from the first and second branchial arches, including antimongoloid slant of palpebral fissures, colobomas of the lower eyelid, eyelash malformations, and malar and mandibular defects. We describe an unusual clinical feature associated with colobomas of the lower eyelids, in a patient with mandibulofacial dysostosis, successfully treated with botulinum toxin and subsequent surgery.

Treacher-Collins syndrome and co-existing dermatomyositis.

BACKGROUND: Treacher-Collins syndrome, an autosomal dominantly inherited malformation of structures derived from the first and second branchial arch, has an incidence of 1:10,000 newborns. The prevalence of dermatomyositis at less than 24 years of age has been estimated at 1 per 100,000. The occurrence of both Treacher-Collins syndrome and dermatomyositis combined in the same patient should occur once in every 1,000,000,000 subjects. METHODS: We report a patient with Treacher-Collins syndrome who developed dermatomyositis at the age of 5 years. RESULTS: No other patient with both Treacher-Collins syndrome and an autoimmune disease has been reported. The thymus originates from the third branchial pouch and is unaffected by the syndrome. In Treacher-Collins syndrome the affected gene has been mapped to the fifth chromosome, while dermatomyositis is related to HLA B8 and DR3, coded on the sixth chromosome. No immunologic alteration has been described in patients with Treacher-Collins syndrome. CONCLUSION: This is the first report of a patient with Treacher-Collins syndrome and dermatomyositis. There is no genetic or physiopathologic explanation for the concurrence of both conditions.