This study examined the epidemiology of Moebius syndrome in a well-defined population over a precise geographical area, using definite diagnostic criteria for MBS. In our series, this disease affects males and females equally, supporting the evidence that MBS is not an inherited X- or Y-related disease, this is an important information to give when physicians are asked about the risk of a second child developing the disease. The non-hereditary nature of this disease is supported by the fact that all cases were sporadic in our series and most reported series. This observation is in line with the recent hypothesis that MBS has a multifactorial basis and genetic mechanisms play a minor role.3-5,12
We found that the overall prevalence of MBS was 0.27/100,000 newborns. We have rounded this value to 0.3/100,000 because a few cases of MBS may have been missed, as some consider this disease shameful and may escape medical notice (and the AISMO database), tending to “self-marginalise”. Regardless, the prevalence observed in our study is much different from prevalences reported in different parts of the world. For example, in the Dutch series, Verzijl et al. estimated a prevalence of 0.002/100,000, which is 100-times rarer than the prevalence reported here; similar prevalences have been reported by physicians with expertise on MBS in the United States, Sweden, and Brazil, but without any epidemiological basis.6-8 From our data, we can conclude that MBS is a rare disease, but not as rare as previously thought; this must be kept in mind when planning healthcare strategies aimed at reducing/ameliorating the social impact and morbidities related this disorder.
Another important consideration is that we found a uniform distribution of MBS cases in the five regions considered. These five regions were conceived by ISTAT, as people living in them have different social, economic, and working lifestyles, with different climates characterizing each region. As we did not identify a region with a higher prevalence of MBS cases, we can exclude environmental factors such as pollution, weather conditions such as intense cold or heat, and prolonged sun exposure during pregnancy as causative for MBS. It appears that the environment had little or no influence on the disease pathogenesis in our population. The only reported agent that significantly increased the risk of newborns being affected by MBS (by a factor of 30) is the use of misoprostol during the first trimester of pregnancy.13 Misoprostol (a synthetic prostaglandin E analogue) is an illegal abortifacient widely used in Brazil and other countries in South and Central America. As misoprostol is not in use in Italy, our epidemiological data on MBS lack any pharmacological bias, at least as far as misoprostol is concerned.
In addition, the patients who were evaluated by our staff after 2007 had an earlier diagnosis than those born before 2007 (2.2 vs. 3.4 years) with a significant reduction in the range, which was lowered to between 0 and 5 years of age. This interesting finding likely resulted from the efforts made during the last two decades by international associations to increase knowledge of this disease; another explanation may be that our specialised medical staff can be contacted easily by relatives of affected newborns, thereby allowing an earlier diagnosis. An early diagnosis of MBS means that we can provide care for affected individuals at a young age. This can have extremely positive effects on the patients’ quality of life by significantly reducing the behavioural and psychological problems related to MBS. For example, with an early diagnosis we can plan smile surgery at a preschool age or we can perform early strabismus surgery when needed, thereby improving visual performance and reducing the risk of amblyopia other than developing the ability to smile.
Our data increase the knowledge of MBS providing its exact epidemiology which may be particularly useful when devising medical policies regarding this rare disease. Most rare diseases are considered “orphans” with no effective treatment; people affected are more vulnerable psychologically, socially, economically, and culturally, as they usually have no response for their medical condition. These difficulties can be overcome and the efforts made by the scientific community can increase our knowledge and give new hope for future treatments of this disorder.