Down Syndrome facial changes are genetic: Research 2023

The Francis Crick Institute, King’s College London, and University College London investigated the genetics behind Down Syndrome mouse model facial and skull changes.

Craniofacial dysmorphology—shortened back-to-front length and enlarged head diameter—was caused by a third copy of Dyrk1a and at least three other genes.

Down Syndrome, a “gene dosage problem,” affects one in 800 newborns. Down Syndrome patients have three chromosomes 21 copies. Three copies of genes on this chromosome cause Down Syndrome-like symptoms, although the genes are unknown.

Genetic engineering was utilized to create mice strains with three duplications on mouse chromosome 16, imitating a third chromosome 21. The mice had Down Syndrome-related facial and skull deformities.

Researchers examined how Dyrk1a, a Down Syndrome gene, affects craniofacial dysmorphology.

They found that mice with an additional copy of Dyrk1a had less cells in the front skull and face bones, working with Jeremy Green’s lab at King’s College London. Synchondroses, skull-base cartilaginous joints, were abnormally fused. Three copies of Dyrk1a are needed to generate these skull modifications, as the third copy partially reversed these effects.

Researchers think a third copy of Dyrk1a slows neural crest cell proliferation, which forms the skull’s front bones.

Three more genes, including Dyrk1a, also cause skull alterations, although further research is needed to identify them.

Victor Tybulewicz, Group Leader of the Down Syndrome Laboratory at the Crick, who worked with first author Yushi Redhead, said: “There’s currently limited treatments for the aspects of Down Syndrome that have a negative impact on people’s health, like congenital heart conditions and cognitive impairment, so it’s essential we work out which genes are important.

Understanding the genetics of head and face development helps us understand Down Syndrome’s heart issues. Dyrk1a is crucial for craniofacial dysmorphology, thus it’s likely involved in other Down Syndrome alterations.

King’s College London researchers employed shape-measuring equipment to map mice’s evolving skulls. These skull alterations resembled Down Syndrome.

Jeremy Green, Professor of Developmental Biology at King’s College London, said, “With the help of great collaborators at the University of Calgary in Canada and a medical imaging software group here at King’s, we were able to apply both quite traditional and some very novel methods for comparing complex anatomical shapes. These detected foetal differences. This helped us locate Down Syndrome genes and understand how they create differences.”

This study is part of Down Syndrome genetics research. Next, the researchers will discover genes linked in cardiac problems and cognitive impairment, bringing us closer to developing targeted treatments for health issues related to Down Syndrome.