Background

Möbius syndrome is due, in part, to loss of function of motor cranial nerves. Although von Graefe described a case of congenital facial diplegia in 1880 , the syndrome was reviewed and defined further by Paul Julius Möbius, a German neurologist, in 1888 and 1892. Because of these contributions, Möbius is now the eponym used to describe the syndrome. p

Möbius Syndrome

Möbius Syndrome

The definition and diagnostic criteria for Möbius syndrome vary among authors. Both von Graefe and Möbius accepted only cases with both congenital facial diplegia and bilateral abducens nerve palsies as constituting M ö bius syndrome. In 1939, Henderson broadened the definition and included cases with congenital unilateral facial palsy.

Other authors are more restrictive in attempts to eliminate conditions of a different pathogenesis being labeled as Möbius syndrome. These investigators require the presence of a congenital musculoskeletal anomaly in order to make the diagnosis. In most studies, Möbius syndrome is defined as congenital facial weakness combined with abnormal ocular abduction.

Pathophysiology

The complete pathophysiological description of Möbius syndrome remains elusive. Whether nerve, brainstem, or muscle aplasia is the primary event has not been established. Nerves that may be involved include cranial nerves (CNs) VI through XII, with general sparing of CN VIII. CN III and CN IV can be involved, but only rarely. The facial nerves (CN VII) are involved in all cases, the abducens nerves (CN VI) in a high percentage of cases (75%), and the hypoglossal nerves (CN XII) in only a minority of cases.

Numerous theories exist concerning the primary underlying pathogenesis. Möbius believed that the condition was degenerative or toxic in origin and that it involved the nuclei of the affected nerves. Some authors suggest that the underlying problem is an inherited congenital hypoplasia or agenesis of the cranial nerve nuclei. Approximately 2% of cases appear to have a genetic basis. In addition, theories of vascular etiologies of the syndrome have many proponents. One such theory involves disruption of flow in the basilar artery or premature regression of the primitive trigeminal arteries. A second vascular theory is a disruption of the subclavian artery supply that involves interruption of the embryonic blood supply. Still others view Möbius syndrome as a mesodermal dysplasia involving musculature derived from the first and second branchial arches. This theory holds that brainstem changes are secondary to retrograde atrophy of the cranial nerves.

Simultaneous limb malformations with cranial nerve dysfunction suggests a disruption of normal morphogenesis during a critical period in the development of the embryonic structures of these regions, most likely at 4-7 weeks of gestation.

Frequency

United States

Möbius syndrome is a rare disorder. Only approximately 300 cases have been described in the English-language literature. The prevalence in the United States is reported as 0.002-0.0002% of births, or 1 case per 50,000 newborns.

International

In a nationwide Dutch survey reported in 2003, the prevalence of Möbius syndrome was at least 0.002% of births (4 cases per 189,000 newborns) for the years 1996-1998.

Mortality/Morbidity

Feeding problems at birth and in infancy may be severe and often are aggravated by associated micrognathia. In severe cases, death may occur in the perinatal period, often as a result of respiratory or bulbar problems. Life expectancy may be normal in patients with less extensive brainstem involvement.

  • In a series from the Hospital for Sick Children in London, England, 8 of 29 patients died over the course of 18 years. All deaths occurred shortly after birth. Four of the deaths were due to respiratory or bulbar problems.
  • Another striking feature causing morbidity in persons with Möbius syndrome is the high incidence of associated congenital deformities. The most common deformity is clubfoot. Brachial deformities and pectoral muscle hypoplasia have been described.
  • A congenital condition called the Poland sequence, characterized by partial or complete absence of the pectoralis muscles and breast and ipsilateral hand malformations, is concurrent with Möbius syndrome in approximately 15% of patients.

Race

No racial predilection is described.

Sex

Both sexes are equally affected.

Age

Möbius syndrome is congenital, and most cases are diagnosed during infancy. The disease is not progressive, and the patient’s presentation is generally based on the severity of the symptoms.

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