Treacher Collins Syndrome

Question 1

What causes treacher collins syndrome?

Answer 1

• caused by abnormal formation of the first and second brachial arches during the 5th-8th week of human fetal development, leading to profound facial dysmorphism
• most cases cuased by loss of function mutations in the gene TCOF1 which encodes the protein Treacle
• other TCS cases caused by mutations to the genes POLR1D and POLR1C which encode subunits of the enzymes RNA polymerase I and III, important in RNA synthesis

Question 2

What are some features of TCS?

Answer 2

• underdeveloped facial bones, particularly cheek bones, eye sockets and a very small chin and jaw (micrognathia)
• some are born with a cleft palate
• underdevelopment of facial bones may cause severe respiratory problems in newborns
• facial features: eyes that slant downwards, sparse eyelashes, eyelid coloboma
• loss of vision and hearing loss - small or unusually formed ears

Question 3

How is TCS treated?

Answer 3

• respiratory failure is main concern
• early intervention to maintain airway, enable feeding, protect the eyes, improve hearing and speech development
• later on aesthetic and functional reconstruction of the mouth, face and external ear may occur
• bone conduction hearing aids or middle ear surgery to improve hearing

Question 4

What is the most common gene mutation causing TCS?

The other gene mutation?

Answer 4

TCOF1 mutations - inherited via autosomal dominant pattern

• POLR1D - autosomal dominant
• POLR1C - autosomal recessive
• some mutations occur spontaneously