title: Mandibulofacial dysostosis (Treacher-Collins syndrome) in the fetus: novel association with Pectus carinatum in a molecularly confirmed case and review of the fetal phenotype.
abstract: BACKGROUND
  Treacher Collins syndrome is the most common mandibulofacial dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case of perinatal death or pregnancy termination.
  
  
  METHODS
  We describe the ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected fetus, and review the clinical, prenatal, and postmortem findings in 15 previously reported fetal and perinatal cases.
  
  
  RESULTS
  A nearly complete spectrum of the typical facial characteristics can be present by the early second trimester of gestation, including subtle defects such as lower eyelid colobomas. Mandibular hypoplasia and bilateral auricle defects were constant findings in the affected fetal population. Downslanting palpebral fissures were the second more common feature, followed by midface hypoplasia, polyhydramnios, and ocular defects. Association with Pierre Robin sequence was common (38%) in the reviewed series. Previously unreported pectus carinatum was noted in our case bearing a heterozygous TCOF1 mutation. Other unique reported findings include salivary gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all in molecularly unconfirmed cases.
  
  
  CONCLUSIONS
  Treacher Collins syndrome can be prenatally detected by ultrasound and should be included in the wide range of genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses tend to have a more severe phenotype than living patients. The reported association of Treacher Collins syndrome type 1 with pectus carinatum expands the phenotype, provides information on genotype-phenotype correlation, and suggests possible pathogenetic interactions between neural crest cell disorders and the formation of the sternum that merit investigation.
authors.affiliation: 1st Department of Pathology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Anastasia E
authors.initials: AE
authors.lastname: Konstantinidou
authors.forename: Jason
authors.initials: J
authors.lastname: Tasoulas
authors.forename: Georgios
authors.initials: G
authors.lastname: Kallipolitis
authors.forename: Spyros
authors.initials: S
authors.lastname: Gasparatos
authors.forename: Voula
authors.initials: V
authors.lastname: Velissariou
authors.forename: Helen
authors.initials: H
authors.lastname: Paraskevakou
mesh_terms: D000328:Adult; D005145:Face / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D005333:Fetus / Q000002:abnormalities*; D005838:Genotype; D006801:Humans; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D016216:Ultrasonography, Prenatal
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human
keywords: Pierre Robin sequence; Treacher Collins syndrome; autopsy; cleft palate; fetus; micrognathia; pectus carinatum; sonography