Möbius Syndrome

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Article initiated by:

Kleonikos A. Tsakiris, MD, MSc, FEBO

All contributors:

Kleonikos A. Tsakiris, MD, MSc, FEBO, Bayan Al Othman, MD, S. Grace Prakalapakorn, MD, MPH, Donny W. Suh, MD, FAAP, MBA, FACS, Marguerite C. Weinert, MD, Kristen Park, MD

Assigned editor:

Marguerite C. Weinert, MD

Review:

Assigned status Up to Date

 by Marguerite C. Weinert, MD on May 29, 2024.

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Möbius Syndrome

DiseasesDB

31978

ICD-10

[1]87.0

OMIM

157900

MeSH

D020331

Möbius syndrome is a congenital condition characterized by strabismus, lagophthalmos, neurodevelopmental abnormalities, autism and sometimes limb and pectoral abnormalities. It is speculated that it results from abnormal vascularization of the brain stem during early intrauterine life, and several mutagens have been incriminated.

Disease Entity

Möbius syndrome (otherwise spelled Moebius syndrome) is a rare congenital disorder that is part of the cranial congenital dysinnervation disorders. It is characterized by non-progressive unilateral or bilateral paralysis of the facial musculature with preservation of the vertical eye movements. The symptoms can be asymmetrical and may vary in severity.

The sixth (CN VI) and the seventh (CN VII) cranial nerves are predominantly affected, resulting in abnormal horizontal gaze and “mask-like facies." Other cranial nerves associated with the disease are the fifth nerve (CN V), the eighth (CN VIII), the tenth (CN X), and the twelfth ( CN XII). When limb abnormalities are also present, the disorder is known as Poland-Moebius Syndrome.

Epidemiology

Exact incidence and prevalence are unknown, but it is thought to affect 1 in 50,000 to 500,000 live newborns. There is no gender predilection. It is thought to be inherited in a sporadic manner.

Etiology

The etiology is poorly understood, but several theories have been posited. The first is the vascular theory, in which plexin D1, a membrane receptor protein that plays a crucial role in proper vascularization of the nervous system during fetal development, is mutated. There is consequently a loss of vascular supply to the neural crests where CN VI and VII nuclei are located, causing improper development of the cranial nerves VI and VII, which are located in a watershed area of the brain stem. The second theory is that of the genetic mutation of the gene PLXND1, which plays a role in the regulation of the migration and proliferation of motor neurons in CN VI and VII. The third theory involves teratogen exposure during the first trimester of pregnancy, specifically, cocaine, ergotamine, benzodiazepines, misoprostol, and thalidomide. These drugs can cause transient ischemia in the brain stem, causing necrosis of cranial nerve nuclei.

Signs & Symptoms

Secondary to CN VI and VII damage, Möbius syndrome presents with “mask-like facies" due to the lack of innervation of the facial muscles as well as inability to abduct the eyes. Other cranial nerves can be involved as well -- namely, CNs XII, V, IX, III, X, VIII, V, IV, and XI. Other associated defects include limb deformities such as clubfoot, ectrodactyly, brachydactyly, syndactyly, arthrogryposis, and congenital amputations. Those affected can also have epicanthic folds, ptosis, external ear defects, tongue atrophy, micrognathia, high-arch hypoglossia, cleft palate, cleft lip, and velopharyngeal insufficiency. Symptoms are bilateral in the vast majority of cases, but unilateral cases have been reported.

Due to these abnormalities, infants with the syndrome have sialorrhea and difficulty feeding. Patients may have coordination or balance difficulties. Additionally, there is mixed evidence that some patients have cognitive impairment, as it is also thought that patients' inability to show emotions may lead to stunted interpersonal relationships.

Clinical diagnosis

Möbius syndrome is primarily diagnosed clinically, and there is currently no universal diagnosis criteria. However, it should be differentiated from isolated cranial nerve palsies.

Staging

According to the National Institute of Neurological Disorders and Stroke there are four categories of Moebius syndrome.

• Group I, characterized by small or absent brain stem nuclei that control the cranial nerves;
• Group II, characterized by loss and degeneration of neurons in the facial peripheral nerve;
• Group III, characterized by loss and degeneration of neurons and other brain cells, microscopic areas of damage, and hardened tissue in the brainstem nuclei, and,
• Group IV, characterized by muscular symptoms in spite of a lack of lesions in the cranial nerve.

Management

There is no cure for Möbius syndrome. Management includes surgical gracilis muscle transfer to restore facial muscle function and allow patients to smile and make other facial expressions. Eye dryness and low blinking rate should be managed by early temporary tarsorraphy. Many ophthalmic surgeons refrain from surgical treatment, but medial rectus muscle recession has been performed, as well as vertical rectus muscle transposition. Because of inconsistent results, surgical options should be explored conservatively. There should be an interdisciplinary approach to management with ophthalmology, plastic surgery, and dentistry.

Additionally, it is advised that patients undergo behavioral therapy to aid in interpersonal communication as patients often experience stigma and bullying both personally and professionally due to their inability to communicate through facial expressions.

Additional Resources

• NIH Neurological Institute. Moebius Syndrome Information Page. The National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Moebius-Syndrome-Information-Page Accessed July 01, 2019.

References

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