What Does “Cause Unknown” Really Mean in Moebius Syndrome?

This is a follow up to my last Blog "Do We Know More About the Cause of Moebius Syndrome Than We Think?"

When I wrote Do We Know More About the Cause of Moebius Syndrome Than We Think?, I was trying to ask a research question. I wanted to know whether the things researchers have already learned about Moebius syndrome might give us clues about what happens during early development.

What I didn’t expect was for some parents to read the article and begin questioning their own pregnancies. A number of people started wondering whether something that happened during pregnancy might have been connected to their child having Moebius syndrome.

That was never the question I was asking, but it made me realize there is another part of this conversation we need to have.

When you have a child with a rare condition and nobody can tell you exactly why it happened, it is understandable to look backward and try to make sense of it. But this is where I think we need to separate what we wonder about from what medicine actually knows.

According to Johns Hopkins Medicine, the primary cause of Moebius syndrome remains unknown, and most cases occur sporadically. Researchers believe that both genetic and environmental factors may play a role, but there is still no single explanation that accounts for everyone with Moebius syndrome.

More recent research says much the same thing. In 2025, researchers from the Grigore T. Popa University of Medicine and Pharmacy in Romania published a review looking at what is currently known about the possible causes of Moebius syndrome. They discussed several different theories, including genetic changes and vascular disruption during early development. Their review made it clear that researchers are still trying to understand the exact biological process that leads to Moebius syndrome.

That is important because when we say the cause is unknown, it does not mean doctors know nothing. We know the basic neurological pattern involved. We know that the sixth and seventh cranial nerve systems are central to classic Moebius syndrome. We also know that researchers have identified genetic changes that may help explain some cases of Moebius syndrome, and that certain prenatal exposures have been associated with a Moebius pattern.

What we do not know is one explanation that fits everybody.

In the previous article, I talked about misoprostol because there is a fairly strong body of research connecting prenatal exposure to misoprostol with some cases of Moebius syndrome. A major study published in the New England Journal of Medicine in 1998 found an association, and later research continued to support it.

The important part of that research, at least to me, is not that misoprostol explains Moebius syndrome. It does not. Moebius existed long before misoprostol did, and most people with Moebius have no known history of prenatal exposure to it.

What makes the research interesting is that it gives us one example where researchers may be able to see part of the biological pathway more clearly. If they can understand exactly how one known exposure sometimes results in a Moebius pattern, perhaps that can help explain cases where no exposure is known.

That is a research question. It is very different from a parent looking backward through a pregnancy and assuming that something they did caused their child’s Moebius syndrome. The research simply does not give us enough information to draw conclusions like that in individual cases.

I think that distinction is very important.

Something happening during pregnancy before a child is born with Moebius does not automatically mean that event caused Moebius. Two things happening during the same period of time is not the same thing as proving one caused the other. That is exactly why medical research looks at larger groups of people, comparison groups and patterns that occur repeatedly.

The comments on the first article did make me think about something else, though. Parents carry a tremendous amount of information about their pregnancies, their child’s birth, medical history and family history. Some parents have told me that nobody ever really asked them about those things after their child was diagnosed with Moebius syndrome.

That surprised me.

I don’t know whether anything parents remember from their pregnancies will ever help researchers understand Moebius syndrome. Maybe it will and maybe it won’t. But I do think those stories are worth listening to. There may be details that were never asked about or documented when their child was diagnosed. Sometimes simply listening to people is where a new question begins.

That is why I think family histories still matter.

Not because parents should be looking for something to blame. Not because MFOMS is trying to determine what caused anyone’s Moebius syndrome. We are not doctors and we are not conducting a medical study.

But the history of Moebius syndrome is also the history of the people and families who have lived with it.

If parents ever want to share the story of their pregnancy, their child’s birth, diagnosis or family history, MFOMS is willing to listen and preserve those stories. Whether they ever point researchers toward something useful is impossible to know. tim@mfoms.org

Maybe they will.

Maybe they won’t.

Either way, they are part of the larger history of Moebius syndrome.

The more I read about this, the more I think the phrase “cause unknown” can be misleading. It can make it sound as though we are standing at the starting line with no information at all.

We are not.

Researchers have learned a great deal about the neurological systems involved in Moebius syndrome. They have identified some possible genetic pathways. They have studied vascular disruption during early development. They have also identified at least one prenatal exposure that has been repeatedly associated with a Moebius pattern in some cases.

There are pieces of the puzzle.

What we do not yet know is exactly how all those pieces fit together, or whether they ever will fit into one single explanation.

Maybe they won’t.

Maybe Moebius syndrome is the end result of several different developmental pathways that eventually arrive at a similar neurological outcome.

That was really the question behind my first article, and it is still the question I find most interesting.

Instead of asking only, “What causes Moebius syndrome?” maybe we should also be asking, “What biological processes can lead to the Moebius pattern, and how many different pathways can get us there?”

That is a very different question from asking what a parent did during pregnancy.

One can lead us toward blame.

The other leads us toward understanding.

And understanding is where I hope this conversation continues to go.

Where This Information Comes From

The medical information discussed in this article comes from established sources including Johns Hopkins Medicine, peer-reviewed research available through PubMed and the National Institutes of Health, the New England Journal of Medicine, and recent scientific reviews examining genetic, vascular and developmental theories of Moebius syndrome.

MFOMS does not provide medical advice and is not conducting medical research through these discussions. Our goal is to make published research easier to understand, listen to the experiences of people affected by Moebius syndrome, and encourage questions that may be useful to future research.