Mobius syndrome is nothing to smile about

Science has an article this week (sadly behind a subscription wall) about a rare disease called Mobius syndrome. Mobius syndrome is a developmental disorder of facial muscle innervation with a variety of presentations; however, the presentation often includes facial paralysis and difficulty in smiling:

The syndrome is named for Paul Julius Mobius, a German neurologist who published an early description of it in 1888. (He was also the grandson of August Ferdinand Mobius, the mathematician of Mobius strip fame.) According to a statement developed at the conference, the syndrome's defining characteristics are facial weakness and impaired ability to move the eyes to the side--symptoms that are present at birth and don't worsen with age. Researchers estimate that Möbius syndrome occurs in 1 of every 50,000 live births, affecting boys and girls equally often.

The core symptoms of Mobius syndrome point to defects in two cranial nerves: the abducens nerve, which innervates the lateral rectus muscles that rotate the eyes toward the side of the head; and the facial nerve, which innervates the muscles of the face. Yet, there doesn't seem to be a single neuropathological signature of the disorder.

At the conference, George Padberg, a neurologist at the University Medical Center in Nijmegen, the Netherlands, described magnetic resonance imaging studies he and colleagues have done to visualize the nervous system in people with Mobius syndrome, as well as findings from electrophysiological tests of nerve function. This work has revealed a variety of defects. In some patients, the cranial nerves appear to be damaged or even missing. Others have abnormalities in the brainstem that include--and often extend beyond--the region where the abducens and facial nerves originate. Based on these and other findings, Padberg suspects that Mobius syndrome results from genetic miscues that derail the embryonic development of the brainstem.

But the search for the relevant genes has yielded little fruit so far. The rarity of the disorder, coupled with the fact that only about 2% of cases are inherited, makes it difficult to find a sufficient number of subjects for genetic linkage studies, says Ethylin Wang Jabs, a geneticist at Johns Hopkins University in Baltimore, Maryland. The complexity of the disorder and lack of precise diagnostic criteria have also complicated matters, Jabs says. Padberg's group, for example, has published studies identifying regions of chromosome 3 and chromosome 10 as likely loci of genes related to inherited Mobius syndrome in two Dutch families, but other researchers point out that individuals in these families lack the eye-movement irregularities necessary to qualify as true cases of Mobius syndrome. (Padberg now agrees.)

Interestingly enough, while it believed that the disease is partly genetic, it may also have a sporadic cause in the use of the drug misoprostol to chemically induce abortion:

Garbled genes aren't the only way to get Mobius syndrome. Since the mid-1990s, dozens of cases of Mobius syndrome have been linked to misoprostol, a drug commonly used by women in Brazil to induce abortion. Elective abortion is illegal in Brazil, but misoprostol is cheap and widely available, says pediatric ophthalmologist Liana Ventura of Fundacao Altino Ventura, a medical charity in Recife, Brazil. Although misoprostol is used in three-quarters of abortion attempts in Brazil, it is not particularly effective: Up to 80% of pregnancies continue to term, and about 20% of those result in an infant with Mobius syndrome, Ventura says. Misoprostol is typically used in the first trimester of pregnancy, and in the sample of Mobius children Ventura has worked with, misoprostol exposure occurred on average about 40 days after conception.

Some researchers have proposed that Mobius syndrome can result from a transient interruption in fetal blood circulation, and Ventura and others think the misoprostol findings fit with that idea. One possibility is that uterine contractions evoked by the drug disrupt fetal blood supply during a crucial stage of development, causing neural circuits in the brainstem to be permanently miswired.

I was reading this article, and it just reminded me that I have a lot of trouble smiling for cameras. No, this is not a neurological disorder, and, no, it is not nearly as debilitating as Mobius syndrome. But it does cause a load of hassle for me. Everyone gives me a hard time about it. I just can't manage to smile on command. (I smile spontaneously all the time.) It is like my brain returns a total failure to compute this command.

At the beginning of the article in Science, they interview a producer at CNN who says that this disorder causes him all sorts of social difficulties because people think he is being serious when he isn't. It really makes you think about the degree to which social interaction is maintained by facial expression, and how horrible it can be to lack the means of that expression.

Anyway, on a lighter note, they mention a plastic surgeon, Dr. Ronald Zuker at the Hospital for Sick Children in Toronto, Canada, who has pioneered a surgery to help kids with this disorder. His procedure moves muscle from the thigh -- the gracilis...a muscle that doesn't really do much in walking -- to the face to help with smiling. The results are dramatic if you keep in mind that particularly for neurological disorders even a small increases in function can result in a large improvement in quality of life.

He published a paper on the procedure in which he shows the following pre-op and post-op pictures (click to enlarge). In both cases the picture on the right is relaxed face; the picture on the left is trying to smile.

Pre-op

Post-op

Neat stuff.

Anyway, the article ended with a quote about how this disorder can sometimes be helpful. The CNN producer interviewed earlier mentions the following:

McCaughan, whose work at CNN has given him the opportunity to travel with and interview several U.S. presidents over the years, says his condition sometimes works in his favor. "I'd say I've got the best deadpan in the business when asking a question."