Mobius Syndrome Workup

Updated: Oct 04, 2018
  • Author: Cheryl Ann Palmer, MD; Chief Editor: Amy Kao, MD  more...
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Approach Considerations

No diagnostic laboratory studies yield findings specific to Möbius syndrome. Imaging studies—specifically, computed tomography (CT) scanning and magnetic resonance imaging (MRI)—may reveal calcifications in the regions of the CN VI nuclei and demonstrate cerebral malformations. Electromyography can be used to help determine whether a patient’s symptoms stem from birth trama and are therefore not associated with Möbius syndrome.


CT Scanning, MRI, and Ultrasonography

Some physicians do not pursue imaging studies of the brain, but many experts recommend them. CT scanning or MRI of the brain may demonstrate bilateral calcifications in the regions of the CN VI nuclei. [30] One report describes bilateral calcifications of the basal ganglia on the brain CT scans of 2 siblings with classic Möbius syndrome. [31] However, these calcifications are not specific for the disease.

It has also been found that, on imaging, the brainstem may appear hypoplastic, with straightening of the fourth ventricular floor. The absence or hypoplasia of CN VI and CN VII may be the most common radiologic features in sporadic Möbius syndrome, and hypoplasia of CN IX may be an associated feature. [32]

Brain MRI may help in determining whether other, perhaps genetically determined, cerebral malformations are present.

Although prenatal ultrasonography is not usually indicated, it has been used to depict basal ganglial and brainstem calcifications in the brains of developing infants.



Some instances of facial palsy occur with birth trauma, especially with the use of forceps in breech deliveries. By definition, traumatic injuries are not part of Möbius syndrome. Timing of the injury to the facial nerve may be important, and electromyography (EMG) can assist in this regard.

Denervation potentials are present only if the facial nuclei or nerves were injured 2-3 weeks or more before the electromyographic study. Facial muscles that are congenitally aplastic or hypoplastic as a result of Möbius syndrome or nerve injury occurring early in gestation do not demonstrate active denervation. This finding can help in differentiating Möbius syndrome from perinatal trauma to peripheral nerves.

In a study of 24 patients with Möbius syndrome, Cattaneo et al found 2 different, defined phenotypes after neurophysiological testing (which included EMG). Based on their EMG data, the authors postulated that the first group had rhombencephalic maldevelopment, while the second group seemed to have acquired a nervous system injury during intrauterine life. [33]

In a study of EMG results from 7 patients with Möbius syndrome, Jaradeh et al suggested that the primary cause of neural involvement was prenatal brainstem damage involving the motor nuclei and their internuclear connections. [34]

The diagnosis of Möbius syndrome soon after birth may be difficult. Möbius syndrome can easily be confused with congenital myopathies, muscular dystrophies, or congenital myotonic dystrophy. If abnormal, EMG findings can help in the differential diagnosis.


Histologic Findings

Few published cases contain pathologic descriptions. Gross findings include asymmetry of the medulla, but the external appearance of the brain generally is normal.

Upon histologic evaluation, the most notable abnormalities have been seen in the motor nuclei of the cranial nerves (CNs), especially in CN VI (see the first image below), CN VII, and CN XII and, to a lesser extent, in CN III and CN XI nuclei. CN VI often shows the most striking changes, with near-total neuronal loss and, sometimes, necrosis (see the second and third images below). The necrotic foci are round, well circumscribed, and basophilic. Degenerative periodic acid-Schiff–positive material may be seen. [6] The necrotic foci may be surrounded by radiating cell processes.

Low-power photomicrograph of a brainstem specimen Low-power photomicrograph of a brainstem specimen in an infant with Möbius syndrome who died at age 3 months. Image shows bilateral lesions in the pons of the abducens nuclei (hematoxylin and eosin stain).
Medium-power photomicrograph from the abducens nuc Medium-power photomicrograph from the abducens nucleus in an infant with Möbius syndrome who died demonstrates diffuse necrosis and neuronal loss (hematoxylin and eosin stain).
High-power photomicrograph shows a lesion of an ab High-power photomicrograph shows a lesion of an abducens nerve nucleus in an infant with Möbius syndrome who died at age 3 months. Image shows neuronal loss, necrosis, myxoid change, and a circumferential rim of thickened glial fibrils (hematoxylin and eosin stain).

Gliosis may be seen in the affected regions, and occasional axonal spheroids have been seen in the periphery of the necrotic lesions. The pyramids may appear underdeveloped. Atrophy of the facial muscles has been described, with adipose and fibrous tissue replacement.


Laboratory Studies

There are no laboratory studies that apply to the majority of Möbius syndrome cases.


Imaging Studies

Imaging studies are not necessary for the diagnosis of Möbius syndrome, but can be helpful to exclude other similar conditions.