Index
Infrequent congenital disorder.
Moebius syndrome is a rare neurological disorder characterized by weakness or paralysis of multiple cranial nerves, most often the sixth and seventh nerves.
Other cranial nerves are sometimes affected. The disorder is present at the time of birth (congenital). If the seventh nerve is involved, the person with Moebius syndrome can not smile, frown, purse his lips, raise his eyebrows or close his eyelids.
If the sixth nerve is affected, the eye can not rotate outward beyond the midline. Other abnormalities include underdevelopment of the pectoral muscles and defects of the extremities.
Moebius syndrome is not progressive. The exact cause is unknown. It seems to occur randomly (sporadically) in most cases; however, some cases occur in families that suggest that there may be a genetic component.
Congenital facial paralysis was first described by Von Graefe (1880) and Moebius (1888), a German neurologist who later named the syndrome.
Signs and symptoms
The anomalies and the severity of Moebius syndrome vary greatly from one person to another:
- Facial paralysis or weakness that affects at least one but usually both sides of the face (seventh cranial nerve).
- Paralysis of the side (lateral movement) of the eyes (sixth cranial nerve).
- Preservation of vertical movements of the eyes. Less frequently, other cranial nerves, including the 5th, 8th, 9th, 10th, 11th and 12th may be affected.
- Babies with Moebius syndrome can drool excessively and show crossed eyes (strabismus). Because the eyes do not move from side to side (laterally), the child is forced to turn his head to follow objects.
Babies who lack facial expression are often described with a face similar to a “mask” that is especially obvious when they laugh or cry.
Affected babies may also have difficulty feeding, including swallowing problems and poor suctioning. Ulceration of the cornea can occur because the eyelids remain open during sleep.
There is a great variety of additional abnormalities. Some children with Moebius syndrome have a short malformed tongue and / or an abnormally small jaw (micrognathia).
The cleft palate may also be present. These anomalies contribute to feeding and breathing difficulties. Children with cleft palate are prone to ear infections (otitis media).
There may be abnormalities in the outer ear, including underdevelopment of the outer portion of the ear (microtia) or total absence of the outer portion of the ear (anotia).
If the eighth cranial nerve is affected, there is likely to be a hearing loss. Dental abnormalities are not uncommon. There is a greater risk of infantile cavities. Some affected children have difficulties with speech and delays in speech development.
Skeletal malformations of the extremities occur in more than half of children with Moebius syndrome.
Malformations of the lower extremities include webbed feet and underdevelopment of the lower legs; the upper extremities may have finger tissue (syndactyly), underdevelopment or absence of the fingers and / or underdevelopment of the hand.
In some children there may be an abnormal side-to-side curvature of the spine (scoliosis), and in about 15% of patients an underdevelopment of the chest (pectoral) muscles also occurs on one side of the body.
Some affected children show delayed achievement of certain milestones such as crawling or walking, most likely due to the weakness of the upper body; however, most children eventually catch up.
Moebius syndrome is rarely associated with a minor intellectual disability. Some children have been classified as on the “autistic spectrum”. The exact relationship between Moebius syndrome and autism is unknown.
Some studies have suggested that autism spectrum disorders occur more frequently in children with Moebius syndrome; Other studies have not confirmed this and suggest that any relationship of this kind is exaggerated.
Moebius syndrome is often associated with a variety of social and psychological consequences. The lack of facial expressions and the inability to smile can cause observers to misinterpret what an affected individual thinks, feels or intends.
Although clinical anxiety and depression are not more common in children and adolescents with Moebius syndrome, affected people can avoid social situations due to apprehension and frustration.
Causes
Most cases of Moebius syndrome occur randomly for unknown reasons (sporadically) in the absence of a family history of the disorder.
The syndrome is listed as Mendelian Online Inheritance in Man (OMIM) number 15700, with a genetic map locus of 13q12.2-q13.
Sporadic mutations have also been identified in the PLXND1 and REV3L genes in a series of patients and it is confirmed that they cause a constellation of findings consistent with Moebius syndrome when introduced in animal models.
In rare cases, familiar patterns have been reported. Most likely, Moebius syndrome is multifactorial, which means that genetic and environmental factors play a causal 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 onset of the disease.
The abnormal gene can be inherited from either parent, or it can be the result of a new mutation (gene change) in the affected individual.
The risk of transmitting the abnormal gene of the affected parent to offspring is 50% for each pregnancy, regardless of the sex of the resulting child.
The spectrum of findings in Moebius syndrome suggests a defect in the development of the rhombencephalon. Several different theories have been proposed to explain the cause of Moebius syndrome.
One hypothesis is that the disorder is the result of decreased or interrupted blood flow (ischemia) to the developing fetus during pregnancy (in the uterus). Recent research suggests that lack of blood affects certain areas of the lower brain stem that contain the cranial nerve nuclei.
This lack of blood flow could be the result of an environmental, mechanical or genetic cause. However, the cause of the syndrome is not conclusive and a more basic and clinical investigation is necessary.
Affected populations
Moebius syndrome affects men and women in equal numbers. The disorder is present at the time of birth (congenital).
The exact incidence and prevalence rates of Moebius syndrome are unknown. One estimate calculates the incidence in 1 case per 50,000 live births in the United States.
Related disorders
The symptoms and signs of the following disorders may be similar to those of Moebius syndrome. The comparisons can be useful for a differential diagnosis.
Several investigators have reported cases in which the characteristics of Moebius syndrome occur in association with the Poland syndrome. This is sometimes referred to as “Poland-Moebius syndrome”.
The syndrome of Poland is characterized by the tissue of the fingers, the absence or underdevelopment of the fingers or hands, and the underdevelopment of the chest muscles. The syndrome of Poland usually occurs only on one side of the body (ipsilateral).
There is a debate within the medical literature about whether Moebius syndrome, the Poland syndrome and the Poland-Moebius syndrome represent three distinct disorders or three different expressions of a disorder.
Congenital hereditary facial paralysis (HCFP) is characterized by isolated paralysis of the facial nerve, and subsets of HCFP have other associated findings, including hearing loss and strabismus.
HCFP differs from Moebius syndrome by the presence of a complete horizontal gaze. HOXB1 mutations have been identified on chromosome 17q21 in patients with HCFP.
Human HOXA1 syndromes are rare disorders with complex neurological and systemic manifestations.
The range and types of clinical findings in affected patients vary widely. Affected people have a phenomenon of Duane (“horizontal gaze paralysis”), which is characterized by the restriction in lateral eye movement.
Hearing loss, developmental delays and a spectrum of the internal carotid artery and conotruncal cardiac malformations have also been documented.
Facial asymmetries and minor malformations of the outer ear are also sometimes present.
Affected people may also show signs of cognitive and behavioral decline and some people have been classified as having autism spectrum disorder.
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.
There are other causes of congenital facial paralysis, in particular, hemifacial microsomia and possibly trauma at birth. There are also acquired types of facial paralysis.
Melkersson-Rosenthal syndrome is characterized by a sudden onset in childhood / adolescence, bilateral or unilateral facial weakness, chronic swelling of the face (especially the lips) and a wrinkled 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 tumors or brain stem damage.
Diagnosis
The diagnosis of Moebius syndrome is based on 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 can be done to rule out other causes of facial paralysis.
Treatment
The treatment of Moebius syndrome is aimed at the specific abnormalities in each individual. Usually, these children are managed by a multidisciplinary team, often in a craniofacial center.
The specialists involved include: pediatricians; neurologists; plastic surgeons; ear, nose and throat specialists (otorhinolaryngologists); orthopedists; dental specialists; speech pathologists; specialists who evaluate and treat hearing problems (audiologists), specialists who treat ocular abnormalities (ophthalmologists) and other health professionals.
Corrective procedures for facial paralysis involve the transfer of muscle and / or graft nerves to another area of the face or body.
An old procedure, known as temporal tendon transfer, involves taking the temporalis muscle, one of the muscles normally used to chew, and transferring it to the corners of the mouth.
This same type of operation can also be used to improve the closing of the eyelids. If the paralysis is only on one side (unilateral), a “nerve graft through the face” is an option. The procedure involves taking a sensory nerve from the calf.
The most recent procedure, called “smile operation,” involves the microvascular transfer of a muscle from the thigh (gracilis) to the face and connects the nerves that normally supply the masseter muscle (one of the muscles used to chew).
This operation has shown remarkable results in terms of speech, facial mobility and self-esteem. Frequent lubrication for dry eyes is often necessary.
Physiotherapy may be necessary for people with various orthopedic abnormalities. Occupational therapy can also 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 corrected surgically, although some doctors recommend delaying these procedures, since sometimes the condition improves with age.
Operations may also be necessary for the various skeletal malformations affecting the extremities and jaws. Specialized procedures are available to correct abnormalities and / or underdevelopment of the chest wall and chest.
Splints, braces and prostheses may be necessary for people with congenital abnormalities of the extremities. Genetic counseling can be beneficial for the people affected and their families.
