Craniofacial anomaly characterized by an antimongoloid slant of the eyes, coloboma of the lid, micrognathia (can be severe), microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present.
First reported in 1846, but associated with British ophthalmologist Treacher Collins after description of two cases in 1900. Further extensively reported by Swiss ophthalmologist Franceschetti and geneticist Klein in 1940s who named it mandibulofacial dysostosis.
Treacher-Collins-Franceschetti Syndrome; Berry-Treacher-Collins Syndrome; Mandibulofacial Dysostosis; TCOF-I Syndrome.
1:25,000 to 1:50,000 live births.
An autosomal dominant transmission with high penetrance and variable expressivity. The gene is localized on the long arm of chromosome 5 (in 5q32-q33.1 locus region, also termed TCOF1 locus) and produces a protein called the “treacle” gene involved in ribosome biogenesis. Mutations of two other genes (POLR1C and POLR1D) are also implicated.
Dysmorphogenesis of the first and second embryonal branchial arch systems. It has been postulated that it results from a defect in a nucleolar trafficking protein that is critically required during human craniofacial development. The facial features are strikingly similar to those observed with vitamin A toxicity in both animals and humans born of a mother who took 2,000 IU of vitamin A daily as a supplement during pregnancy.
The diagnosis of these syndromes is based on the clinical features. The radiographic studies may show poorly developed supraorbital ridges, hypoplastic malar bones, hypoplasia of mandible, and flat or aplastic coronoid and condyloid processes. Prenatal diagnosis is possible by ultrasonographic examination (by the 20th week) and by molecular biology on chorionic villus sample (as source of fetal DNA). All the mutations currently reported suggest haploinsufficiency as the molecular mechanism underlying the disorder. Laboratory and radiological findings, which include supraorbital ridges, hypoplastic malar bones, hypoplasia of mandible, aplastic coronoid and condyloid processes, and abnormal cranial base (basilar kyphosis).
The eyes show several anomalies: antimongoloid obliquity of palpebral fissures, coloboma of outer portion lower lids, with a deficiency of cilia, absence of the lower lacrimal points, microphthalmia. Flattening of the cheeks. Facial features: malar hypoplasia; hypoplastic zygomatic arches; antimongoloid slant; lower eyelid coloboma; microphthalmia; vision loss; strabismus; partial absence of lower eyelashes; nystagmus; atresia of external auditory meatus; microtia; malpositioning or maldevelopment of the pinna. Mouth: cleft palate, mandibular hypoplasia, macrostomia, absence of parotid gland. Other clinical anomalies: cardiovascular defects; cervical vertebral malformations; renal anomalies; choanal atresia; limb malformations; early failure to thrive; chronic respiratory insufficiency; cryptorchidism; psychological problems and social stigma as a consequence of facial deformity; sleep apnea syndrome and sudden death; conductive hearing loss. Intellectual disability in only 5% of patients if hearing ...