Moebius Syndrome

The classic form of Moebius syndrome is caused by damage cranial nerves VI and VII, also known as the abducens and facial nerve, respectively. The facial nerve is responsible for controlling the muscles in charge of facial expressions, while the abducens nerve controls the eye muscle that allows us to move the eyes laterally. More complex cases of Moebius syndrome may involve other cranial nerves and have associated facial and limb deformities. 

It is thought that damage to the cranial nerves occurs during fetal development. While the exact cause is not fully understood, it may be related to decreased blood supply to the brainstem during cranial nerve development. Other theories suggest there may be an underlying genetic predisposition and several pathogenic variants have been identified (e.g., PLXND1 and REV3L gene mutations), however, Moebius syndrome doesn’t typically run in families. In the rare cases of familial transmission, Moebius syndrome is inherited in an autosomal dominant pattern, meaning that one copy of the altered gene needs to be passed down to cause the condition.  

The classic manifestations of Moebius syndrome include facial paralysis and limited outward movement of the eyes. Facial paralysis causes weakness in one or both sides of the face, which can result in a lack of facial expression, including smiling, frowning, or blinking the eyes. Weakness of the muscles around the eyes can cause incomplete closure of the eyelids during sleep, which may lead to corneal ulcerations. Affected individuals may also have difficulty with speaking and eating, including swallowing problems and impaired sucking. A decreased coughing reflex and laryngeal paralysis originating from other cranial nerve palsies can further worsen the condition, as there is an increased risk of aspiration when swallowing food, liquids, or saliva.  

People with Moebius syndrome cannot typically move their eyes to the side due to abducens nerve palsy, and therefore are forced to turn their heads to the side to follow objects. A classic feature of Moebius syndrome is that vertical eye movement is preserved, which means individuals have no difficulty looking up or down. Many individuals also have strabismus, most commonly esotropia, when one or both eyes turn inward toward the nose. Esotropia can interfere with social interactions and decrease the visual field and depth perception, which can contribute to a delay in reaching motor skills for children.  

In addition to the classic manifestations, there can be many other signs and symptoms. For example, individuals may have characteristic facial features, such as a short tongue, jaw deformities, and cleft palate, which is when the palate contains an opening into the nose. There can also be a low muscle tone (i.e., hypotonia) and limb deformities, such as clubbed feet and underdevelopment of the lower legs and arms, as well as webbing or absence of one or more fingers.  

Finally, children with Moebius syndrome usually do not have intellectual disabilities, however, there may be a delay in reaching developmental milestones like sitting, walking, or speaking. Some research suggests a higher rate of autism spectrum disorder (ASD) in children with Moebius syndrome, however, some of the symptoms of Moebius syndrome (e.g., lack of facial expression, limited eye movement, speech delays) could be mistaken for ASD symptoms, which is why a careful evaluation is needed to distinguish between the two conditions.   

Currently, there is no cure for Moebius syndrome. Management involves a multidisciplinary team of neurologists, orthopedic surgeons, ophthalmologists, and plastic and reconstructive surgeons to manage the various signs and symptoms.  

To improve feeding, infants with Moebius syndrome may benefit from the use of specialized feeding bottles which decrease sucking effort and simulate breastfeeding. In severe cases, nutritional support with artificial feeding may be needed to ensure adequate nutrition. Depending on the specific needs of the individual, a feeding tube may be inserted through the nose into the stomach (i.e., NG tube) or directly into the stomach (i.e., G tube) or intestines (e.g., I or J tube) through the abdominal wall.  

Surgical procedures to correct facial weakness can allow individuals to improve facial movements and facial symmetry. Similarly, surgery can be done to correct esotropia or misalignment of the eyes. Additionally, surgery and orthopedic aids may be necessary for skeletal defects affecting the limbs and jaws. Finally, children with Moebius syndrome may benefit from early intervention programs to improve speech, swallowing, and motor skills coordination. These programs may include a combination of speech therapy, and physical and occupational therapy, depending on the specific needs of the individual.