Treacher Collins Syndrome

Question 1

what is the incidence rate of TCS?

Answer 1

1:50000

Question 2

what causes TCS?

Answer 2

abnormal formation of the first and second branchial arches

Question 3

what weeks of development are effected in TCS?

Answer 3

5-8

Question 4

what gene if effected and how?

Answer 4

loss-of-function mutations in the gene TCOF1

Question 5

what does TCOF1 encode?

Answer 5

treacle protein

Question 6

what is underdeveloped in most cases?

Answer 6

facial bones
cheek bones
eye sockets
jaw and chin
ears

Question 7

what are facial features?

Answer 7

eyes slant downwards
sparse eyelashes
eyelid coloboma

Question 8

what are complications?

Answer 8

loss of vision
loss of hearing

Question 9

what early intervention is needed?

Answer 9

clear and maintain airway
enable feeding
protect eyes
improve hearing
speech development

Question 10

what is the most common gene mutation?

Answer 10

TCOF1 mutation via autosomal dominant pattern

Question 11

what are the uncommon mutations?

Answer 11

POLR1D POLR1C mutations by autosomal dominant and recessive patterns

Question 12

what are the majority of the TCOF1 mutations?

Answer 12

deletions (1-40 nucleotides)

Question 13

what do TCOF1 mutations result in?

Answer 13

truncated treacle protein which is small and non-functional

Question 14

what is the role of treacle protein?

Answer 14

active during early embryonic development in structures that become bones and other facial tissues

key role in pre-ribosomal processing and making of the ribosome

Question 15

what does haploinsufficiency of TCOF1 result in?

Answer 15

depletion of NCC precursors so less NCC migrating to developing craniofacial complex