Down’s syndrome, also known as trisomy 21, is a relatively common genetic condition that includes characteristic craniofacial traits, developmental delays, and intellectual impairments. Affected individuals inherit an extra copy of chromosome 21 at conception, an example of aneuploidy—when cell division results in the wrong number of chromosomes—or three copies of chromosome 21 instead of two. The proper separation of chromosomes during cell division is an active area of research for Investigators Jennifer Gerton, Ph.D., and Scott Hawley, Ph.D. While typically associated with increased maternal age, recent findings from the Gerton Lab identified the mechanism behind a common chromosomal rearrangement called Roberstonian chromosomes as an age-independent cause for Down’s. Currently, there is no cure for Down’s syndrome, yet early intervention therapies enable individuals to lead happy, healthy, and productive lives.

Treacher Collins syndrome (TCS) is a rare craniofacial condition characterized by abnormalities of facial cartilage and bone affecting the ears, eyes, cheekbones, and chin. Symptoms can range from mild to severe where some individuals may have difficulties breathing, seeing, and hearing. Most frequently, individuals with TCS have a mutation in a gene involved in forming ribosomes. Disruptions in ribosome production can trigger cell death of critical developmental cells called neural crest cells, many of which migrate to the head and face during early development. While the only available treatments are reconstructive surgery, speech therapy, and hearing aids, Investigator Paul Trainor, Ph.D., is studying the cellular, molecular, and genetic mechanisms implicated in TCS with the hope to uncover ways to reduce its severity and potentially prevent the condition.

Cornelia de Lange syndrome is a rare genetic condition with characteristic craniofacial features and often accompanied by additional physical and cognitive difficulties. Hundreds of genetic mutations have been identified with most affecting a protein complex called cohesin. Cohesin helps fold DNA into loops, holds replicated chromosomes together, facilitates genetic exchanges between them, and keeps chromosome centers organized and aligned for proper cell division. While the only available treatments involve surgery and physical and occupational therapy, the origins of this condition are active areas of scientific inquiry. Investigator Jennifer Gerton, Ph.D., uncovered that along with genetic mutations, disfunctions of the placenta may also contribute to severity of the condition in mouse systems that may enable targeted treatments.

This genetic condition occurs when nerve cells of the gut fail to form and is linked to mutations in multiple genes, causing an abnormally large colon, digestion difficulties, and delays in growth. Investigator Paul Trainor, Ph.D., studies how certain genetic mutations disrupt the migration of neural crest to the intestines. Commonly, surgical intervention is necessary to remove the part of the affected colon. However, Trainor believes there may be ways to identify supplements akin to folic acid that have the potential to prevent neural crest cell death, in Hirschsprung’s disease, Treacher Collins syndrome, and other congenital craniofacial conditions.

Cleft lip and palate are some of the most common craniofacial conditions affecting around 1 per 750 births. Both genetic and environmental factors have been linked to these conditions and can be traced to disruption of neural crest cells. Standard treatment is surgical correction shortly after birth, however cleft lip and cleft palate frequently accompany more severe congenital conditions like Treacher Collins syndrome and Cornelia de Lange syndrome.