• Unilateral or bilateral facial weakness with impairment of ocular abduction
– Other cranial nerves may be involved
– Limb anomalies may be present
0.0002–0.002% of live births (1)
• Estimated 2,000 living cases worldwide (2)
• Estimated 800 living in the US (2)
• Family history of Moebius or possibly other overlapping congenital cranial dysinnervation disorders (CCDD)
• Multiple teratogens have been suggested (1)
– Gestational hyperthermia
– Electric shock
– Chorionic villus sampling
– Abuse of benzodiazepines
• Autosomal dominant, autosomal recessive and X-linked recessive have been reported.
• Variable expression and penetrance
– MBS1 (13q12.2–q13) involved in two unrelated families (1)
– MBS2 (3q21–q22) and MBS3 (10q21.3–q22.1) await confirmation (1)
– Multiple chromosomal aberrations known to have Moebius as a feature
• Avoidance of in utero exposure to known teratogens.
• Genetic counseling
• Not completely understood but felt to be secondary to rhombencephalic maldevelopment involving predominantly motor nuclei and axons traversing long tracts (3)
– Complex disruption of development thought to occur between 21–34 days of embryogenesis (4)
– Exposure to teratogens
COMMONLY ASSOCIATED CONDITIONS
• Crenulations on sides of tongue/hypoplasia (75%): Involvement of cranial nerve XII
• Craniofacial malformations: Epicanthal folds, flat nasal bridge, micrognathia, high arched palate, external ear defects, teeth defects, and hypertelorism (90%)
• Malformations of extremities (85%)
• Feeding problems (86%)
• Duane syndrome (34%)
• Poland syndrome (11%)
– Rare associations: Congenital heart defects, dextrocardia, arthrogryposis multiplex, urinary tract anomalies, anosmia, and hypogonadotropic hypogonadism (3)
• Family history
• Known exposure to teratogen in utero
• Other known associated anomalies
• Complete ocular examination
– Evaluate ocular motility and alignment (usually orthophoric in primary position)
– Evaluate weakness of orbicularis oculi (involvement of cranial VII)
– Evaluation of ocular surface
– Assessment of visual function
– Evaluate external structures for craniofacial findings
– Complete systemic evaluation for associated anomalies
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• None required
• Consider karyotype/microarray if no teratogen is identified. Gene testing not yet available specifically for Moebius, although testing of other genes known to be causative of CCDD may have a role.
Follow-up & special considerations
Consider evaluation for mitochondrial disorder including Kearn Sayres with chronic progressive ophthalmoplegia (acquired), if history of congenital involvement unclear.
• No imaging is necessary
– MRI of head may be performed to evaluate cranial nerves and nuclei
• Isolated cranial nerve 6 palsy
• Esotropia with pseudo-abduction deficit (especially with congenital/infantile esotropia)
• Other oromandibular limb hypogenesis syndromes: Hypoglossia-hypodactylia syndrome, Hanhart syndrome, glossopalatine ankylosis syndrome
• Chronic progressive external ophthalmoplegia and other mitochondrial disorders
• Thyroid eye disease
• Intranuclear ophthalmoplegia
• Ocular lubricants as needed for ocular surface drying
• Artificial tear ointment at bedtime or taping lids close may be helpful in cases of lagophthalmos
Amblyopia therapy as needed
Issues for Referral
• These patients have multiple system involvement and often need multidisciplinary approach
– Nutritionists, occupational therapist for feeding issues
– Orthopedist, physical and occupational therapist for limb anomalies
– Speech pathologist for language delay
– ENT for tracheostomy if unable to manage their secretion
– Dentist for teeth anomalies
– Neuropsychologist is often helpful
– Genetic counseling
Bandage contact lenses may be useful in the treatment of extreme corneal involvement from exposure.
COMPLEMENTARY & ALTERNATIVE THERAPIES
• Surgery for esotropia may be performed as needed
– Temporary tarsorrhaphy for extreme exposure may be beneficial
• Frequent follow-up required if ocular surface drying is present.
• As needed for amblyopia monitoring and treatment
• Visual function and school performance
• Overall health and development of child
• Attention to concerns about self image
Adjust as needed in view of possible swallowing issues.
• Genetic counseling
• Family support network: Moebius Syndrome Foundation (www.moebiussyndrome.com)
• Moebius is a nonprogressive congenital condition
– With good supportive care, normal life expectancy
• Corneal ulceration and/or perforation
1. Briegel W. Neuropsychiatric findings of Mobius sequence – a review. Clin Genet 2006;70:91–97.
2. Broussard AB, Borazjani JG. The faces of Moebius syndrome: Recognition and anticipatory guidance. Am J Matern Child Nurs 2008;5:272–278.
3. Verzijl HT, van der Zwaag B, Cruysberg JR, Padberg GW. Moebius syndrome redefined: A syndrome of rhombencephalic maldevelopment. Neurology 2003;61:327–333.
4. Miller MT, Owens P, Chen F. Mobius and Mobius-like syndromes. J Pediatr Ophthalmol Strabismus 1989;26:176–189.