What are other Names for this Condition? (Also Known As/Synonyms)

• Congenital Facial Diplegia
• Mobius Syndrome
• Moebius Sequence

What is Moebius Syndrome? (Definition/Background Information)

• Moebius Syndrome is an extremely uncommon neurological disorder that involves either the 6^th cranial nerve (abducens nerve) or the 7^th cranial nerve (facial nerve) or both. It results in the weakening and paralysis of the facial muscles
• In most cases, the condition causes difficulty in eyelid movement and an inability to form facial expressions. In some cases, Moebius Syndrome can also cause other physical defects involving the chest or limbs. However, intellectual growth and development is generally not hindered
• The cause of Moebius Syndrome is presently unclear, but certain cases are reportedly inherited. Most cases are sporadic in nature and the risk factors are unknown. Researchers have implicated certain genetic mutations and/or a lack of blood supply to the fetus during pregnancy as probable explanatory factors for underdevelopment of the involved cranial nerves
• The treatment measures for Moebius Syndrome are directed towards addressing the signs and symptoms and different complications that develop in the individual. The outcome for individuals with Moebius Syndrome is dependent on the severity of the condition

Who gets Moebius Syndrome? (Age and Sex Distribution)

• The number of cases of Moebius Syndrome worldwide is unknown. However, it is an extremely rare disorder
• It is a congenital condition, meaning that it is almost always manifested at birth
• Moebius Syndrome is seen in both males and females at equal incidence
• Worldwide, no increased prevalence in any specific racial or ethnic group is observed

What are the Risk Factors for Moebius Syndrome? (Predisposing Factors)

• A few cases of Moebius Syndrome have been seen to run in families (positive family history)
• The risk factors for the syndrome are mostly related to genetics

It is important to note that having a risk factor does not mean that one will get the condition.  A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors.  Some risk factors are more important than others.  

Also, not having a risk factor does not mean that an individual will not get the condition.  It is always important to discuss the effect of risk factors with your healthcare provider.

What is the Cause of Moebius Syndrome? (Etiology)

Currently, there is no definite cause identified for Moebius Syndrome. It is genetic condition that occurs randomly in many individuals; no clear inheritance pattern is also observed.

• There is an underdevelopment of the 6^th and 7^th cranial nerves that controls eye movement and facial expressions respectively. To describe this, multiple proposals have been placed forward including:
  • Mutations involving the PLXND1 and REV3L genes
  • Lack of blood supply (ischemia) to the fetus while in the womb, leading to an underdeveloped brainstem. The brainstem is the location of the nuclei for the nerves that are affected in Moebius Syndrome
  • In sporadic cases, the cause could be a combination of the above factors, or even unidentified (idiopathic)
• All of the above-mentioned factors, can lead to underdeveloped and defective cranial nerves, especially involving the abducens and facial nerves, resulting in a set of accompanying signs and symptoms
• In rare case of a positive family history of the condition, Moebius Syndrome follows an autosomal dominant inheritance pattern

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Moebius Syndrome?

The signs and symptoms of Moebius Syndrome depend on the nerve(s) affected. It may vary in severity from one child to another and can be mild or severe.

• When the abducens nerve is affected, the following may be noted:
  • The individual may have difficulty moving their eyes from side to side
  • Vertical movement of the eyes is normal
  • The cornea of the individual can be damaged due to problems closing eyes or squinting
  • One may not even be able to close the eyelids
• When the facial nerve is affected, the following may be noted:
  • The individual may have difficulty smiling, puckering their lips, raising the eyebrows, and even frowning
  • Either one side or both sides of the face is affected
  • Facial expressions and display of emotions will be minimal to absent
• Other abnormalities may include:
  • A small chin and mouth
  • Shortened and misshapen tongue
  • Cleft palate: Having an opening in the roof of the mouth
• Difficulty chewing and swallowing can also be noted
• Limb defects: Shortened or misshapen arms and legs may be noted in some children

How is Moebius Syndrome Diagnosed?

A diagnosis of Moebius Syndrome may involve:

• Physical examination and assessment of the presenting signs and symptoms
• Review of the individual’s medical and family history 
• Neurological examination of the individual
• Prenatal ultrasound scans may reveal fetal abnormalities
• Other investigative procedures, such as blood tests and imaging scans, may be undertaken as needed

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible complications of Moebius Syndrome?

Depending on the severity of Moebius Syndrome, numerous complications affecting various parts of the body (present from birth) may be noted. The complications may include:

• Slow muscle growth leading to delays in achieving growth milestones such as crawling, walking, etc.
• Slow growth of the outer ear or lack of an outer ear
• Difficulty hearing or total loss of hearing
• Increased risk for teeth deformities and cavities
• Many individuals with Moebius Syndrome also display signs of autism
• Decreased quality of life

It is difficult to determine what complications an individual may develop or display.

How is Moebius Syndrome Treated?

Currently, there is no cure for Moebius Syndrome. The treatment is focused on limiting the effects of the complications associated with the condition.

• Nerve/muscle transplants and grafts: Functional nerves and muscles from other parts of the body are placed in the regions that are dysfunctional. This have proven to be an effective treatment for individuals with Moebius Syndrome. However, not all motor issues typically observed in the disorder are resolved
• Physical therapy from a young age is an effective method to increase development of the motor skills that are lacking
• Occupational therapy for older individuals is also known to be beneficial
• Speech therapy can help individuals overcome certain jaw and mouth (motor) issues
• Braces to correct or aid in walking
• Surgery to correct minor or severe abnormalities

How can Moebius Syndrome be Prevented?

At the present time, there are no prevention methods available for Moebius Syndrome, particularly for sporadic cases. In case of a positive family history, the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis for Moebius Syndrome? (Outcomes/Resolutions)

• The prognosis for individuals with Moebius Syndrome typically depends on the signs and symptoms and complications noted
• Individuals with mild signs and symptoms have better prognosis than those with severe ones

Additional and Relevant Useful Information for Moebius Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/