OMIM ID:
Treacher Collins-Franceschetti Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Lid fissures often have an antimongoloid slant. Many patients (69%) have a coloboma of the lower eyelid (in contradistinction to Goldenhar spectrum syndrome [164210] in which the lid colobomas involve the upper eyelid) with a paucity of lashes and meibomian glands medially. Colobomas may also involve the iris, choroid and optic nerve. Other ocular features include blepharoptosis, hypoplasia of the supraorbital ridges, absent lacrimal puncti, underdevelopment of the orbicularis oculi muscle, absence of the tarsal plate, and abnormalities of the lateral canthal tendons. Strabismus and amblyopia have been reported in a significant number of individuals.
Systemic Features
A variety of defects in facial development have been reported, most involving the ears, eyelids, lower jaw, and zygomatic arch. The characteristic facial phenotype is usually evident at birth. One-third of patients have a cleft palate. Microtia or even anotia may be present and a conductive hearing loss can result, especially when the ossicles are malformed or absent. The pinnae are often malformed, appearing ‘crumpled’, low-set, and rotated posteriorly. There may be ear tags and blind fistulas anywhere between the tragus and angle of the mouth. The mandible and its rami may be hypoplastic causing severe micrognathia that can result in feeding and speaking difficulties, especially when pharyngeal hypoplasia is also present. The zygomatic arches are often underdeveloped (or even absent) and the midface is flattened. Arhinia and cleft palate are sometimes seen. A low hairline may be present. Intelligence is usually normal.
Genetics
Inheritance
This is an autosomal dominant syndrome secondary to mutations in the TCOF1 gene located at 5q32-q33.1. A parental gender influence is suggested by at least one study which found an increase in the number of affected offspring from affected mothers compared with those from affected fathers. Many cases (60%) result from new mutations but a paternal age effect has not been established. Inter- and intrafamilial clinical variation is wide.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission