We’re excited to share the results of a 10-year genetics research study, funded in part by the Moebius Syndrome Foundation, that is now published in Genetics in Medicine Open!

This study included 149 individuals with Moebius syndrome – the largest study to date of Moebius syndrome. Most participants (73.8%) were enrolled at Moebius Syndrome Foundation family conferences.

Who was included in the study?
The researchers used very strict criteria for a diagnosis of Moebius syndrome to distinguish Moebius syndrome from related facial weakness conditions.

Everyone in the study had both:

• Facial weakness (difficulty smiling) from birth
• Limited outward eye movement (trouble moving the eyes away from the nose)

To keep the group focused, participants were excluded from this study if they:

• Had significant trouble looking up (especially before any eye surgery), or
• Had both trouble looking up and droopy eyelids.

What did the study find?

The study helped expand what we know about the clinical features of Moebius syndrome. Common traits found in participants included:

• Small tongue (81.9% of participants)
• Small lower jaw (66.4% of participants)
• Clubfoot (42.3% of participants)
• Major limb differences (31.5% of participants)
• Intellectual disability (30.9% of participants)
• Sleep difficulties (22.8% of participants)
• Poland syndrome (14.1% of participants)

Researchers also found that Moebius syndrome does not appear to be caused by changes in the germline DNA—the genetic material we are born with and can pass on to our children.

The study also did not find mutations in the PLXND1 or REV3L genes in any of the study participants. These genes had been suggested in earlier studies to cause Moebius syndrome, but this research shows they are not common causes of Moebius syndrome and may only be involved in very rare cases—or not at all.

What this means for the Moebius syndrome community is that people with Moebius syndrome are unlikely to pass Moebius syndrome to their offspring. Parents of children with Moebius syndrome are unlikely to have more than one child with Moebius syndrome.

The researchers now believe the cause may involve other possibilities, like rare gene changes that happen randomly (after conception), or developmental changes early in pregnancy. More research is still needed.

These findings will help doctors better diagnose and care for people with Moebius syndrome.

We would like to thank the researchers who have dedicated their efforts to studying Moebius syndrome and all the families who made this study possible.

The research team includes:

• Dr. Ethylin Wang Jabs (Mount Sinai, Mayo Clinic)
• Dr. Bryn Webb (Mount Sinai, University of Wisconsin)
• Dr. Elizabeth Engle (Boston Children’s Hospital)
• Dr. Irini Manoli and Dr. Francis Collins (NIH)

We appreciate all of the donors who financially contributed towards this research and the Moebius Syndrome Foundation.

This work will be discussed at our upcoming conference in Salt Lake City! In-person participants may submit questions during the discussion and speak directly with the researchers behind this work. The discussion will be recorded and posted on our website after the conclusion of the conference.

Read the full paper

Download the PDF inforgraphic