For Medical Professionals

Diagnosing Moebius Syndrome

Moebius syndrome may require a co-diagnosis across neurology, ophthalmology, and genetics. Neurology will need to assess nerve structure, ophthalmology will confirm lack of eye movements, and genetics will rule out known genetic facial paralysis conditions. Our Scientific Advisory Board offers expert knowledge on Moebius syndrome. Please feel free to reach out to these individuals for questions and concerns related to the condition.

Please refer newly diagnosed patients to the Moebius Syndrome Foundation website and encourage them to join our community in order to receive a free welcome packet and more information about Moebius syndrome.

What are the basic criteria for diagnosing Moebius syndrome?

Moebius syndrome is defined by 1) congenital, non-progressive facial weakness with 2) limited outward horizontal movement of one or both eyes. These two features must be present to have a diagnosis of Moebius syndrome. An additional criterion of having full vertical (up and down) eye movement, prior to any eye surgery, has also been suggested.

The symptom of facial weakness is due to abnormal development or function of the facial nerve (cranial nerve 7). The symptom of limited outward horizontal eye movement is due to a problem with the abducens nerve (cranial nerve 6).

Facial weakness caused by Moebius syndrome may present on one (unilateral) or both (bilateral) sides of the face.

Moebius syndrome may affect other cranial nerves (typically the lower ones, such as nerves 9, 11, and 12) in addition to nerves 6 and 7.

Moebius syndrome has a variety of facial presentations

How often does Moebius syndrome occur?

Our current best estimate for the incidence of Moebius syndrome is roughly 2 to 20 cases per million births. Moebius syndrome occurs equally in all populations. The condition occurs in all ethnicities. There is no gender bias; males and females are affected equally.

What is the cause of Moebius syndrome?

The cause of Moebius syndrome is not well understood. Genetic research into the condition has not shown a clear genetic pattern. 

While there are some conditions with overlapping features to Moebius syndrome that may run in families, in our MSF-supported studies, no individuals with classic Moebius syndrome have more than one affected family member in their families.

Some research completed in Europe with lead authors from the Netherlands has suggested that gene changes in two genes (PLXND1 and REV3L) may cause Moebius syndrome, but we have been unable to identify additional patients with changes in these two genes in the United States.

Moebius syndrome-like conditions may occur from fetal exposure to misoprostol and/or other drugs that cause constriction of blood vessels. However, it is important to understand that environmental exposure to drugs causes a minority of cases with Moebius syndrome.

Some medical literature has theorized that reduced blood flow, or vascular interruption, may contribute or be the cause of Moebius syndrome.

Additional research is ongoing to further investigate the etiology of Moebius syndrome.

Why is it called Moebius syndrome?

Moebius syndrome was originally described by German ophthalmologist Alfred Graefe in 1880, but it’s named for German neurologist Paul Julius Moebius, who reported features of this condition in 1888.

Additional Clinical Presentations

Moebius syndrome may occur with other clinical symptoms, including: 

  • Strabismus (cross-eyes or misalignment of the eyes), which may develop over time and not be present at birth
  • Hearing loss
  • Club foot
  • Poland anomaly (underdevelopment of the chest wall muscle, webbed fingers, and a small hand)
  • Limb differences (hand, foot, or other limb anomalies)
  • Muscular hypotonia (low muscle tone)
  • Congenital heart disease
  • Developmental delay (delayed timing to reach milestones such as independent sitting, walking, and/or speech)
  • Autism
  • Intellectual disability
  • Dental concerns
  • Sleep disorders

Cognitive development is normal in most cases of Moebius syndrome.  When intellectual disability is present, affected persons also tend to have additional clinical features such as congenital heart disease, cleft palate, and other systemic involvement.

Similar Facial Palsy Conditions

Genetic research into Moebius syndrome has identified other genetic conditions with clinical features overlapping with that of Moebius syndrome. They are:

  • Mutations in the gene named TUBB3: In addition to congenital facial palsy, TUBB3 presents with both restricted vertical gaze and limited horizontal eye movement. Persons diagnosed with a TUBB3 mutation have ptosis, or droopiness of the eyelids.
  • Carey-Fineman-Ziter syndrome: Includes facial weakness, full eye movements, and cleft palate with a small chin (Pierre-Robin sequence), and/or hypotonia (muscle weakness). This syndrome is due to changes in the gene named MYMK and is a muscle condition (myopathy), not a condition of the cranial nerves.
  • STAC3 disorder (also known as Native American myopathy): This disorder presents with low muscle tone, facial weakness, contractures, and/or skeletal differences.  This disorder is also a muscle disease (myopathy) and not a condition of the cranial nerves.

This list is not inclusive of all congenital facial weakness conditions. Please refer to “A Framework For the Evaluation of Patients With Congenital Facial Weakness” by Dr. Bryn D. Webb, et al. for more detailed information on the types of congenital facial weakness disorders. The Fig. 1 image may be particularly useful in directing a diagnosis.

Support, events, and information from the Moebius Syndrome Foundation are open to individuals with any form of congenital facial weakness, regardless of genetic cause or official diagnosis. Please refer newly diagnosed patients to our website and encourage them to join our community in order to receive a free welcome packet and more information about Moebius syndrome.

July 2023

A Guide for For Healthcare Providers

Check out our new guide designed specifically to help medical professionals better understand and support patients with Moebius syndrome. The guide is available for download below, or if you live in the United States, you can request that a physical copy be mailed to you by emailing

The cover of the Guide for Healthcare Providers


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Webb BD, Manoli I, Engle EC, Jabs EW. A framework for the evaluation of patients with congenital facial weakness. Orphanet J Rare Dis. 2021 Apr 7;16(1):158. doi: 10.1186/s13023-021-01736-1. PMID: 33827624; PMCID: PMC8028830.

Webb BD, Shaaban S, Gaspar H, Cunha LF, Schubert CR, Hao K, Robson CD, Chan WM, Andrews C, MacKinnon S, Oystreck DT, Hunter DG, Iacovelli AJ, Ye X, Camminady A, Engle EC, Jabs EW. HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/-mice2012 Jul 13;91(1):171-9. doi: 10.1016/j.ajhg.2012.05.018. Epub 2012 Jul 5. PMID: 22770981; PMCID: PMC3397264.

Picciolini O, Porro M, Cattaneo E, Castelletti S, Masera G, Mosca F, Bedeschi MF. Moebius syndrome: clinical features, diagnosis, management and early intervention. Ital J Pediatr. 2016 Jun 3;42(1):56. doi: 10.1186/s13052-016-0256-5. PMID: 27260152; PMCID: PMC4893276.