Treacher Collins syndrome is the prototypical mandibulofacial dysostosis syndrome, but other mandibulofacial dysostosis syndromes have been described. We report an infant with mandibulofacial dysostosis with an apparently balanced de novo 46,XX,t(2;17)(q31;q24) translocation. This 4-month-old girl was the product of a dizygotic twin gestation conceived through intracytoplasmic sperm injection. The twin was unaffected. The affected girl presented with severe lower eyelid colobomas requiring skin grafting, malar and mandibular hyoplasia, bilateral microtia and hearing loss, bilateral choanal stenosis, cleft palate without cleft lip, several oral frenula of the upper lip/gum, and micrognathia requiring tracheostomy. A CT scan of the temporal bones revealed bilateral osseous external auditory canal atresia with associated hypoplasia of the middle ear cavity, dysplasia of the ossicles, and oval window atresia. The limbs were normal. Chromosome analysis at the 650-band level showed a 46,XX,t(2;17)(q31;q24) karyotype. Sequencing of the entire TCOF1 coding region did not show evidence of a sequence variation. Genomic microarray analysis using a 1 Mb human BAC chip did not identify a cryptic imbalance. The facial features are consistent with a mandibulofacial dysostosis that resembles Treacher Collins syndrome, but several features, including the oral frenula, nasal configuration, and severe lower lid ablepharon, are distinctive. The vast majority of individuals with classic Treacher Collins syndrome have mutations in the TCOF1 gene encoding treacle. The lack of an identifiable TCOF1 mutation suggests that this is a provisionally unique mandibulofacial dysostosis syndrome. Treacher Collins syndrome is not typically thought to be genetically heterogeneous, but a small percentage of individuals do not have TCOF1 mutations. The apparently balanced de novo t(2;17)(q31;q24) translocation provides a clue for potential loci for atypical and TCOF1 mutation-negative cases of Treacher Collins syndrome. We hypothesize that disruption of a gene(s) at the 2q and/or 17q breakpoint regions produced the described phenotype in this patient.
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