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Treacher-Collins syndrome

Orpha number ORPHA861
Synonym(s) Franceschetti-Klein syndrome
Mandibulofacial dysostosis without limb anomalies
Prevalence 1-9 / 100 000
Inheritance Autosomal dominant
Autosomal recessive
Age of onset Neonatal
ICD-10
  • Q75.4
ICD-O -
OMIM
UMLS
  • C0242387
  • C0265241
MeSH -
MedDRA
  • 10051456

Summary

Treacher-Collins syndrome is a congenital disorder of craniofacial development characterized by bilateral symmetrical oto-mandibular dysplasia without abnormalities of the extremities, and associated with several head and neck defects.

Annual incidence at birth is estimated at 1/50,000 live births.

Children present with characteristic facial dysmorphism with bilateral and symmetrical hypoplasia of the malar bones and infra-orbital rim (80% of cases) and of the mandible (78%) (retrognathia, retrogenia), which results in dental malocclusion, often characterized by an anterior apertognathia (also called ''open bite"). Predominant hypoplasia of soft tissues is observed in the malar bone, inferior orbital rim and cheek. Features also observed include complex abnormalities in the temporo-mandibular joint leading to a limitation of mouth opening of varying severity, anti-mongoloid obliquity of palpebral fissures (89%) and a coloboma of the lower eyelids between the external and middle thirds (69%) with absence of eyelashes on the outer third of the lower eyelid. The palate is ogival and cleft palate is occasionally observed (28%). External ear abnormalities, such as microtia or anotia, atresia of the external auditory canal and anomalies of the ossicular chain are often present (60%) and lead to conductive hearing loss. Intelligence is usually normal. Breathing and nutrition difficulties may arise during the early years because of the narrowness of the upper respiratory tract and limited mouth opening. Less common signs include enchondromas and/or pretragal fistulas, spinal and cardiac anomalies, and bilateral commissural clefts.

The syndrome is caused by mutations in the TCOF1 gene (5q32) encoding the nucleolar phosphoprotein Treacle or in the POLR1C (6p21.1) or POLR1D (13q12.2) genes, coding for RNA polymerase I and III subunits.

Diagnosis is based on clinical findings and complementary examinations. Molecular tests confirm the diagnosis.

Differential diagnoses include Nager and Miller syndromes and Goldenhar syndrome (see these terms), in its bilateral and slightly asymmetrical form.

Antenatal diagnosis is possible by molecular analysis of chorionic villus samples (CVS). Antenatal ultrasound may show typical facial dysmorphism and bilateral ear abnormalities.

Transmission is autosomal dominant with 90% penetrance and variable expressivity, even among affected patients within the same family. Mutations in POLR1C gene are inherited in autosomal recessive manner. Genetic counseling is complicated by the variable expression of the disease and should be discussed with a multidisciplinary antenatal diagnosis team.

Management is multidisciplinary. In cases with postnatal respiratory distress, tracheostomy, non-invasive ventilation (NIV) or mandibular distraction should be discussed. Maxillofacial and plastic surgery can correct the soft tissue hypoplasia (facial recontouring with lipostructure), bone hypoplasia (surgical bone distraction, bone grafts), eyelid coloboma and cleft palate (surgical repair). The treatment of the limited opening of the mouth is very difficult. Specialist ENT surgery is required for the abnormalities of the middle ear (functional surgery) and the external ear (reconstruction of the auricles). Management of hearing impairment should be early (hearing aids and functional surgery) to aid normal development.

The prognosis for milder forms of the disease is favorable with adequate treatment.

Expert reviewer(s)

  • Pr Marie-Paule VAZQUEZ

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Detailed information

Summary information
Practical genetics
  • EN (2009,pdf)
Article for general public
  • FR (2013,pdf)
Clinical genetics review
  • EN (2012)
Disability factsheet
  • FR (2013,pdf)
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