Mobius syndrome is a very rare congenital disorder characterized by palsies of various cranial nerves, most commonly of the facial and abducens nerves. Main symptoms, developing as early as infancy and during the neonatal period, are incomplete lip closure, poor facial expression, and a fixed eye gaze, together with facial and limb abnormalities. The diagnosis primarily rests on clinical criteria, as the exact etiology of Mobius syndrome remains unknown. Familial cases have been described.
Mobius syndrome (MS) is considered to be a rare disorder in clinical practice, with estimated incidence rates of 1 in 250,000 births . The exact cause of this syndrome, as well as its pathogenesis, remain unknown, with current hypotheses involving genetic mutations and pathological events during embryogenesis    . Although familial cases exist, most cases develop Mobius syndrome sporadically and the clinical presentation may be visible from neonatal period  . The most important features of MS are palsies of the facial (VII) and abducens (VI) cranial nerves  . Reduced facial mimicry (expression during smiling and crying are particularly affected) appearing either in a unilateral or bilateral fashion, and feeding difficulties due to incomplete lip closure that impairs sucking are main signs of facial nerve palsy  . Conversely, abducens nerve palsy is associated with a range of ocular abnormalities, as palsies of other cranial nerves responsible for innervating the ocular muscles (the oculomotor and the trochlear, or III and IV, respectively)  . Commonly reported findings are a fixed gaze, strabismus (either convergent or divergent), defects in abduction/adduction, and ptosis   . Additionally, hypoplasia of the tongue (hypoglossal nerve palsy), speech difficulties, and impaired swallowing (stemming from trigeminal, glossopharyngeal and/or vagus nerve palsies) are also reported in many patients  . Furthermore, cranial nerve palsies are accompanied by anatomical changes of the face (micrognathia, microphthalmia, smaller ears, a bifid uvula) and the musculoskeletal system (torticollis, syndactyly, brachydactyly, clubfoot, and muscular agenesis, particularly of the chest wall)    . Finally, studies identified autism and mental retardation in up to a third of cases .
Entire Body System
Brain stem necrosis resulting from a vascular deficiency has been offered as a possible pathogenetic explanation.(2) The strabismus in Möbius syndrome is congenital esotropia with bilateral limitation in abduction. [ncbi.nlm.nih.gov]
Strabismus surgery in children with Mobius syndrome. J AAPOS. 2000;4:58–59. doi:10.1016/S1091-8531(00)90014-4 [CrossRef] Sun LL, Gole GA. Augmented vertical rectus transposition for the treatment of strabismus in Mobius syndrome. [healio.com]
deformities Claw hands Claw-hand deformities Split-hand [ more ] 0001171 Sporadic No previous family history 0003745 Syndactyly Webbed fingers or toes 0001159 [rarediseases.info.nih.gov]
One common association is the Möbius-Poland anomaly, in which the facial and gaze abnormalities are accompanied by absence of one pectoral muscle with or without ipsilateral hand deformity (12, 13). [neuroophthalmology.ca]
Musculoskeletal involvement included thoracic anomalies observed in 5 %, absence or hypoplasia of pectoralis major muscle in 3 %, chest, arms and hand deformities in 14 %, clubfeet in 32 %, and scoliosis in 6 %. [ijponline.biomedcentral.com]
impairment Deafness Hearing defect [ more ] 0000365 High palate Elevated palate Increased palatal height [ more ] 0000218 Hypogonadotrophic hypogonadism 0000044 Microdontia Decreased width of tooth 0000691 Micrognathia Small lower jaw Small jaw Little [rarediseases.info.nih.gov]
Motor delays due to upper body weakness • Absence of lateral eye movement • Absence of blinking • Strabismus (crossed eyes) • Drooling • High palate • Short or deformed tongue • Limited movement of tongue • Submucous cleft palate • Dental problems • Hearing [thesun.co.uk]
Face, Head & Neck
A 4-year-old boy presented with mask-like facies noted at birth after a 34-week pregnancy. Examination revealed bilateral facial and abducens nerve paralysis with no other neurological abnormalities. [ncbi.nlm.nih.gov]
The main nerves affected are the sixth (CN VI) and the seventh (CN VII) which results in abnormal gazing and mask like facies. [eyewiki.aao.org]
80%-99% of people have these symptoms Abnormality of the voice Voice abnormality 0001608 Facial palsy Bell's palsy 0010628 Feeding difficulties in infancy 0008872 Mask-like facies Expressionless face Lack of facial expression Mask-like facial appearance [rarediseases.info.nih.gov]
neck Decreased length of neck 0000470 Short phalanx of finger Short finger bones 0009803 Split hand Claw hand Claw hand deformities Claw hands Claw-hand deformities Split-hand [ more ] 0001171 Sporadic No previous family history 0003745 Syndactyly Webbed [rarediseases.info.nih.gov]
Additional unusual features were short neck and torticollis. Computed tomography (CT) of the craniocervical region was the imaging of choice, and features compatible with occiput-atlas developmental defect and a hypoplastic atlas were identified. [doi.org]
Cranial Nerve Involvement
Lower cranial nerve involvement, leading to respiratory, swallowing, and cardiac difficulties, was also present. Pathologic examination of the brainstem showed absent or hypoplastic third, seventh, tenth, and twelfth nerve nuclei. [ncbi.nlm.nih.gov]
In addition to the 2 above strict clinical criteria, additional signs or symptoms may also be present, including, but not limited to: – Other cranial nerve involvement – Strabismus (misalignment of the eyes) – Hearing loss – Club foot – Limb reduction [moebiussyndrome.org]
Table 4 Functional symptoms according to specific cranial nerve involvement Cranial nerve involvement V, VII, IX, XI, XII VII, VIII, IX, X, XI, XII III, IV, VI, VII Functional Deficit Poor neonatal sucking and swallowing 37,8 Hearing loss 6,8 Ocular motor [ijponline.biomedcentral.com]
Brainstem dysgenesis: report of five patients with congenital hypotonia, multiple cranial nerve involvement, and ocular motor apraxia. Dev Med Child Neurol 2003; 45: 489-93. 11. [neurologia.com]
Because of the rare occurrence of Mobius syndrome, the diagnosis may be difficult to make, especially in cases with milder phenotypes. For this reason, a detailed history that will assess the main symptoms, as well as their onset and severity (the parents are often the most reliable source, as young children are the main patient population) must be obtained. The physical examination, however, which allows the physician to identify signs of cranial nerve palsies and facial/musculoskeletal abnormalities, is the critical part of the diagnostic workup. A complete inspection of the body and a comprehensive neurological workup are key components. MS remains a diagnosis on clinical grounds, but imaging studies of the brain, such as magnetic resonance imaging (MRI), can provide additional clues by detecting hypoplasia of cranial nerves, their nuclei and their branches  . Calcifications of the brainstem have also been reported on computed tomography (CT) by isolated studies . Despite the fact that certain genetic mutations have been revealed in patients with MS   , specific genetic tests are yet to be designed.
- Picciolini O, Porro M, Cattaneo E, et al. Moebius syndrome: clinical features, diagnosis, management and early intervention. Ital J Pediatr. 2016;42:56.
- Tomas-Roca L, Tsaalbi-Shtylik A, Jansen JG, et al. De novo mutations in PLXND1 and REV3L cause Möbius syndrome. Nat Commun. 2015;6:7199.
- Kumar D. Moebius syndrome. J Med Genet. 1990;27(2):122-126.
- Patel RM, Liu D, Gonzaga-Jauregui C, et al. An exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a TUBB3 mutation. Cold Spring Harb Mol Case Stud. 2017;3(2):a000984.
- Strömland K, Sjögreen L, Miller M, et al. Mobius sequence--a Swedish multidiscipline study. Eur J Paediatr Neurol. 2002;6(1):35-45.
- Carta A, Mora P, Neri A, Favilla S, Sadun AA. Ophthalmologic and Systemic Features in Möbius Syndrome An Italian Case Series. Ophthalmology. 2011;118:1518–1523.
- Abramson DL, Cohen MM Jr, Mulliken JB. Möbius syndrome: classification and grading system. Plast Reconstr Surg. 1998;102(4):961-967.
- Wu SQ, Man FY, Jiao YH, Xian JF, Wang YD, Wang ZC. Magnetic resonance imaging findings in sporadic Möbius syndrome. Chin Med J (Engl). 2013;126(12):2304-2307.
- Dooley JM, Stewart WA, Hayden JD, Therrien A. Brainstem calcification in Möbius syndrome. Pediatr Neurol. 2004;30(1):39-41.