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NORD is very grateful to John B. Mulliken, MD, Director, Craniofacial Centre, Department of Plastic Oral Surgery, Boston Children’s Hospital, for assistance in the preparation of this report.
Moebius syndrome is a rare neurological disorder characterized by weakness or paralysis (palsy) of multiple cranial nerves, most often the 6th (abducens) and 7th (facial) nerves. Other cranial nerves are sometimes affected. The disorder is present at birth (congenital). If the 7th nerve is involved, the individual with Moebius syndrome is unable to smile, frown, pucker the lips, raise the eyebrows, or close the eyelids. If the 7th nerve is affected, the eye cannot turn outward past the midline. Other abnormalities include underdevelopment of the pectoral muscles and defects of the limbs. Moebius syndrome is not progressive. The exact cause is unknown. It appears to occur randomly for unknown reasons (sporadically) in most cases; however, some cases run in families suggesting that there may be a genetic component.
Moebius syndrome is named after Paul Julius Mobius, a German neurologist, who first described the disorder in 1888. There has been disagreement in the medical literature as to a precise definition of the disorder.
The abnormalities and severity of Moebius syndrome can vary greatly from one person to another. Facial paralysis or weakness usually affects both sides of the face (diplegia). The 7th cranial nerve, which controls facial movements, is affected in all cases. The 6th cranial nerve, which controls eye movements, is affected in approximately 75% of cases. Less often, other cranial nerves, including the 5th, 8th, 9th, 10th, 11th, and 12th may be affected.
Infants with Moebius syndrome may drool excessively and exhibit crossed eyes (strabismus). Because the eyes do not move from side-to-side (laterally), the child is forced to turn the head to follow objects. Infants who lack facial expression and are described as having a "mask-like" face that is especially obvious when laughing or crying. Affected infants may also have difficulties feeding, including problems swallowing and poor sucking. Corneal ulceration may occur because the eyelids remain open during sleep.
There are a wide variety of additional abnormalities. Some children with Moebius syndrome have a short, malformed tongue and or an abnormally small jaw (micrognathia). Cleft palate may also be present. These abnormalities contribute to feeding and breathing difficulties. Children with cleft palate are prone to ear infections (otitis media). There may be external ear anomalies including underdevelopment of the outer portion of the ear (microtia) or total absence of the outer portion of the ear (anotia). If the 8th cranial nerve is affected, there is likely hearing loss. Dental abnormalities are not uncommon. Some affected children have difficulties with speech and delays in speech development.
Skeletal malformations can also occur including clubbed feet, underdevelopment of the lower legs, and abnormal side-to-side curvature of the spine (scoliosis). Affected individuals may also have webbing of the fingers (syndactyly), underdevelopment or absence of the fingers, and/or underdevelopment of the hand. In approximately, 15% of cases underdevelopment of the chest (pectoral) muscles and the breast on one side of the body may also occur (see Poland-Moebius syndrome in the Related Disorder section below).
Some affected children exhibit delays in attaining certain milestones such as crawling or walking, most likely due to upper body weakness; however, most children eventually catch-up. Moebius syndrome rarely is associated with minor intellectual disability. Some children have been classified as being on the autistic spectrum. The exact relationship between Moebius syndrome and autism is unknown. Some studies have suggested that autism spectrum disorders occur with greater frequency in children with Moebius syndrome; other studies have not demonstrated this and suggest that any relationship is overstated. Moebius syndrome is often associated with a variety of social and psychological consequences. The disorder can impact an individual’s quality of life. The lack of facial expressions and the inability to smile can cause observers to misinterpret what an affected individual is thinking or feeling or intends. Affected individuals may avoid social situations due to anxiousness and frustration.
Most cases of Moebius syndrome occur randomly for unknown reasons (sporadically) in the absence of a family history of the disorder. In rare cases, familial patterns have been reported. Most likely, Moebius syndrome is multifactorial, which means that both genetic and environmental factors play some causative role. It is possible that in different cases there are different underlying causes (heterogeneity).
In familial cases, there is evidence that Moebius syndrome is inherited as an autosomal dominant trait. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Several different theories have been proposed to explain the cause of Moebius syndrome. One hypothesis is the disorder is the result of diminished or interrupted blood flow (ischemia) to the developing fetus during pregnancy (in utero). Recent research suggests that the lack of blood affects certain areas of the lower brainstem that contain the cranial nerve nuclei. This lack of blood flow can result from an environmental, mechanical or genetic cause. Nevertheless, the underlying cause of Moebius syndrome remains inconclusive and more basic and clinical research is necessary.
Moebius syndrome affects males and females in equal numbers. The disorder is present at birth (congenital). The exact incidence and prevalence rates of Moebius syndrome are unknown. One estimate places the incidence at 1 case per 50,000 live births in the United States.
Symptoms and signs of the following disorders can be similar to those of Moebius syndrome. Comparisons may be useful for a differential diagnosis.
Several investigators have reported cases in which the features of Moebius syndrome occur in association with Poland syndrome. This is sometimes referred to as "Poland-Moebius syndrome". Poland syndrome is characterized by webbing of the fingers, absence or underdevelopment of the fingers or hands, and underdevelopment of the chest muscles and breast. Poland syndrome usually occurs on only one side of the body (ipsilateral). There is debate within the medical literature as to whether Moebius syndrome, Poland syndrome and Poland-Moebius syndrome represent three distinct disorders or three different expressions of one disorder. (For more information on this disorder, choose "Poland" as your search term in the Rare Disease Database.)
Human HOXA1 syndromes are rare disorders with complex neurological and systemic manifestations. The range and types of clinical findings in affected patients vary significantly. Affected individuals present with Duane phenomenon and/or "horizontal gaze palsy", both of which are characterized by restrictions in lateral eye movements. Hearing loss, developmental delays, and a spectrum of internal carotid artery and conotruncal heart malformations also have been documented. Facial asymmetries and minor external ear malformations are also sometimes present. Affected individuals can also show signs of cognitive and behavioral impairments and some individuals have been classified as on the autism spectrum disorder (ASD). The abnormal gene has been identified and its location on chromosome 7 has been determined. Human HOXA1 syndromes are inherited as autosomal recessive genetic conditions. (For more information on this disorder, choose "HOXA1" as your search term in the Rare Disease Database.)
There are other causes of congenital facial paralysis, in particular, hemifacial microsomia and possibly secondary to birth trauma. There are also acquired types of facial palsy. Melkersson-Rosenthal syndrome is characterized by sudden onset in childhood/adolescence, of bilateral or unilateral facial weakness, chronic swelling of the face (especially the lips) and a furrowed tongue. Other possible causes are: infections such as Ramsay-Hunt syndrome; systemic and neurological disorders including cerebral palsy, congenital muscular dystrophy, spinal muscular atrophy, Guillain-Barre syndrome, multiple sclerosis and autoimmune disorders; brain trauma; and brainstem tumors or damage. (For more information on this disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
A diagnosis of Moebius syndrome is based upon the characteristic signs/symptoms, a detailed patient history, and a thorough clinical evaluation. There are no diagnostic tests that confirm a diagnosis of Moebius syndrome. Some specialized tests may be performed to rule out other causes of facial palsy.
The treatment of Moebius syndrome is directed toward the specific abnormalities in each individual. Usually these children are managed by a multidisciplinary team, often in a craniofacial center. Involved specialists include: pediatricians; neurologists; plastic surgeons; ear, nose, and throat specialists (otolaryngologists); orthopedists; dental specialists; speech pathologists; specialists who assess and treat hearing problems (audiologists), specialists who treat eye abnormalities (ophthalmologists) and other healthcare professionals.
Reconstruction procedures for facial paralysis involve transfer of muscle and/or graft nerves from another area of the face or the body. An old procedure, known as temporalis tendon transfer, involves taking the temporalis muscle, one of the muscles normally used for chewing (mastication), and transferring it to the corners of the mouth. This same type of operation can be also used to improve closure of the eyelids. If the paralysis is on only one side (unilateral), a "cross-facial nerve graft" is an option. The procedure involves taking a sensory nerve from the calf, attaching it to a branch of the functioning facial nerve on the normal side of the face and then waiting until the regenerating nerve fibers cross over the face to reach the paralyzed side where it is joined to a motor nerve of a thin muscle transferred to the face by microvascular anastomosis.
The most recent procedure, called "the smile operation", involves microvascular transfer of a muscle from the thigh (gracillis) to the face and connecting the nerves that normally supply the masseter muscle (one of the muscles used for chewing). This operation has shown remarkable results in terms of speech, facial mobility and self-esteem. Frequent lubrication for dry eyes is often necessary.
Physical therapy may be needed for individuals with various orthopedic abnormalities. Occupational therapy may be beneficial, especially in patients with abnormalities of the hands, fingers and toes. Speech therapy may be necessary for some affected children. Strabismus is usually surgically correctable, although some physicians recommend delaying these procedures as the condition sometimes improves on its own with age. Operations may also be necessary for the various skeletal malformations affecting the limbs and jaws. Specialized procedures to correct abnormalities and/or underdevelopment of the chest wall and breast are available.
Splints, braces and prostheses may be necessary for individuals with congenital limb abnormalities. Genetic counseling may be of benefit for affected individuals and their families.
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Report last updated: 2013/01/28 00:00:00 GMT+0