By Liji Thomas, MD
Treacher-Collins syndrome, also called mandibulofacial dysostosis (MFD1), is a genetic disorder causing the abnormal development of the bones that make up the lower part of the face. Affecting 1 in 50,000 people, the syndrome results in some or all of the following:
- a small lower jaw and receding chin (technically called micrognathia)
- a very large mouth
- eyes that slant downwards
- scanty eyelashes along the lower eyelid
- tiny, absent or severely malformed outer ears
- a notch in the lower eyelid, called a coloboma
- a low scalp hairline reaching up to the cheekbones
- palatal abnormalities in two-thirds of affected children ( one-third have a cleft palate and the rest show a fixed or shortened palate)
- swallowing and speech problems due to abnormal palate development
- loss of vision
- hearing difficulty in up to half of affected individuals, due to a defective ear canal or malformed bones in the middle ear
Treacher-Collins syndrome affects both males and females alike. The manifestations may vary from very mild or almost unnoticeable at birth, to severe. This condition is also called Franceschetti-Zwahien-Klein syndrome or Treacher-Collins-Franceschetti syndrome.
Treacher-Collins syndrome is due to a mutation in a gene that regulates the synthesis of ribosomal RNA (rRNA). This affects the formation of the proteins that make up the bones of the face. The TCOF1 gene is involved in up to 93% of all affected people.
Other genes such as the POLR1C or POLR1D gene are affected but much less frequently. The TCOF1 or POLR1D gene mutation is an autosomal dominant one. Therfore a single copy of a mutated gene in a cell will produce disease manifestations, even if the second copy is normal. Even though this is a genetic condition, no other family member is affected in 60% of these cases. This means the mutation has emerged newly in the affected individual, with the parents being absolutely normal. In the remaining, the mutant gene is inherited from an affected parent.
When the POLR1C gene is affected it causes an autosomal recessive pattern of inheritance, which means both copies of the gene must be abnormal for the disease to manifest. If only one copy is present, the affected person is a carrier of the defective gene but does not show any physical signs. Both parents of children with Treacher-Collins due to POLR1C mutation have one defective copy of the gene but are physically normal. However, in most cases of Treacher-Collins, the mutation is not inherited, but can be passed on to the offspring.
Diagnosis and treatment
Children with Treacher-Collins syndrome are easily diagnosed in most cases because of their characteristic facial abnormalities. They have normal intelligence. Their main difficulties lie in normal feeding, swallowing and speech, because of the presence of a cleft palate and hearing loss.
Treatment is directed towards correcting the practical difficulties of the child. There may be severe airway obstruction due to the poor growth of the facial bones. This may require tracheostomy for several years. Treatment is also required to correct the hearing loss, which may be severe, and adjusting the facial profile. This may require extensive and repeated plastic surgery. Genetic counseling is advisable before affected people attempt to conceive. Prenatal diagnosis is not yet commonly available.
Last Updated: Apr 19, 2015