Orofacial clefts (OFCs) are structural birth defects which occur when a baby’s lip or mouth does not form properly during pregnancy and are some of the most common birth defects. Children with OFCs often have hearing loss, dental problems, and difficulties with eating and speaking. Identifying genetic factors contributing to OFCs could help improve diagnostics, treatments, and outcomes of OFCs.

Children with OFCs also have an increased risk of developing certain types of cancers (like breast, brain, and colon cancers), suggesting a shared genetic pathway between these disorders. The NIH Common Fund’s Gabriella Miller Kids First Pediatric Research (Kids First) Program is helping scientists improve our understanding of the connection between structural birth defects and childhood  cancer by developing a large-scale database of genetic and clinical data from patients and their families with these conditions.                       
Scientists participating in the Kids First Program used genetic data accessible through the Gabriella Miller Kids First Data Resource Portal, to pinpoint a new gene region linked to the risk of OFCs on chromosome 21, near genes involved in facial development. This genetic study of OFCs is the first to involve large enough numbers of patients and their relatives to allow meaningful results.   

The researchers analyzed genetic data from 580 OFCs patients and their families of European and Colombian descent. The newly identified region on chromosome 21 is part of a larger region that had been previously reported in studies of people of European descent, but not those of Latin American descent, suggesting that genetic differences within a population could influence the risk of development of OFCs.

Identifying risk genes is often the first step to understanding a disease and allows for the development of novel therapeutic approaches. Further studies are needed to determine the biological impact of this newly identified gene region. Findings like these could help guide scientists to other genes that play a role in the relationship between structural birth defects and childhood cancer, as well as lead to the discovery of shared genetic pathways between these disorders. 

Reference

Mukhopadhyay, N., Bishop, M., Mortillo, M. et al. Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21. Hum Genet 139, 215–226 (2020). https://doi.org/10.1007/s00439-019-02099-1.