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2023 ACMG Annual Clinical Genetics Meeting Digital ...
TCOF1
-related Treacher Collins syndrome: ...
TCOF1
-related Treacher Collins syndrome: Report of a clinically unaffected parent with mosaicism
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Pdf Summary
Treacher Collins syndrome (TCS) is a genetic disorder characterized by craniofacial abnormalities such as micrognathia and malar hypoplasia. It is caused by disruptions in the TCOF1, POLR1D, POLR1B, POLR1C pathway. This pathway is responsible for proper development of neural crest cells. TCS can be inherited in an autosomal dominant or recessive manner and may show reduced penetrance and clinical variability.<br /><br />This case report describes a one-day-old male with severe micrognathia and mandibulofacial dysostosis. He had other dysmorphic features such as sparse hair, small lower eyelid colobomas, downslanting and narrow palpebral fissures, bilateral microtia, bulbous nose, and severe maxillary mandibular hypoplasia. The patient had a complicated prenatal course with polyhydramnios and intrauterine growth restriction.<br /><br />Genetic testing revealed a heterozygous pathogenic variant in the TCOF1 gene. Interestingly, the variant was also identified in the father's buccal cells, indicating mosaicism. Mosaicism refers to the presence of a genetic mutation in only a portion of an individual's cells. This is the first reported case of a clinically unaffected individual with mosaicism of a TCOF1 pathogenic variant.<br /><br />The presence of mosaicism suggests that some level of loss or compensation is occurring, resulting in unobservable features of the disease. This highlights the importance of genetic testing and trio sequencing, when possible, in order to provide accurate counseling and recurrence risks to families affected by TCS.<br /><br />In conclusion, this case report adds to the limited knowledge about mosaicism in TCS and emphasizes the significance of genetic testing in diagnosing and understanding genetic disorders like TCS.
Asset Subtitle
Presenting Author - Laura Cross, MS, CGC; Co-Author - Joseph T. Alaimo, PhD, FACMG; Co-Author - Shivarajan M. Amudhavalli, MD;
Meta Tag
Congenital Anomaly
Counseling
Dysmorphology
Etiology
Exome sequencing
Genetic Diversity
Genetic Testing
Inheritance Patterns
Molecular Pathophysiology
Phenotype
Risk Assessment
Sequencing
Co-Author
Joseph T. Alaimo, PhD, FACMG
Co-Author
Shivarajan M. Amudhavalli, MD
Presenting Author
Laura Cross, MS, CGC
Keywords
Treacher Collins syndrome
craniofacial abnormalities
micrognathia
malar hypoplasia
TCOF1
genetic testing
mosaicism
genetic counseling
recurrence risks
genetic disorders
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