What causes Treacher-Collins syndrome?

• A. Reduced migration of neural crest cells to the first and second pharyngeal arches
• B. Mutation in neural growth factor
• C. Decreased neural tube development
• D. Exposure to teratogens in the first trimester

Answer: (A)

Treacher-Collins syndrome arises from reduced migration of neural crest cells to the first and second pharyngeal arches. Neural crest cells migrate into these arches early in development and give rise to much of the midface, including the maxilla, zygomatic bones, mandible, and several ear structures. When their migration is impaired, the facial bones and related tissues fail to develop normally, leading to the characteristic features such as malar hypoplasia, micrognathia, and ear anomalies. In many cases this is linked to mutations in the TCOF1 gene, which affect neural crest cell survival during this critical period, reinforcing the importance of this migratory process. Other options describe mechanisms that cause different conditions—mutations in a neural growth factor would imply a distinct pathway, decreased neural tube development leads to neural tube defects, and teratogen exposure can disrupt development in various ways but does not specifically explain the neural crest–driven facial dysostosis seen in Treacher-Collins.