eMedicine Specialties > Neurology > Pediatric Neurology
Mobius Syndrome: Differential Diagnoses & Workup
Updated: Mar 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Abducens (CN VI) nerve palsy
Asymmetric crying facies
Brainstem syndromes
Duane syndrome
Kallmann syndrome
Metabolic neuropathy
Myotonic diseases
Neuromuscular diseases
Poland anomaly
Klippel-Feil anomaly
Workup
Laboratory Studies
No diagnostic laboratory studies yield findings specific to Möbius syndrome.
Imaging Studies
Some physicians do not pursue imaging studies of the brain, but many experts recommend them.
- CT scanning or MRI of the brain may demonstrate bilateral calcifications in the regions of the CN VI nuclei.
- The brainstem may appear hypoplastic with straightening of the fourth ventricular floor.
- One report describes bilateral calcifications of the basal ganglia on the brain CT scans of 2 siblings with classic Möbius syndrome.23 These calcifications are not specific for the disease.
- Brain MRI may help in determining whether other, perhaps genetically determined, cerebral malformations are present.
- Although not usually indicated, prenatal ultrasonography has depicted basal ganglial and brainstem calcifications in the brains of developing infants.
Other Tests
Electromyography
- Some instances of facial palsy occur with birth trauma, especially with the use of forceps in breech deliveries. By definition, traumatic injuries are not part of Möbius syndrome. Timing of the injury to the facial nerve may be important, and electromyography (EMG) can assist in this regard.
- Denervation potentials are present only if the facial nuclei or nerves were injured 2-3 weeks (or more) before the study. Facial muscles that are congenitally aplastic or hypoplastic as a result of Möbius syndrome or nerve injury occurring early in gestation do not demonstrate active denervation. This finding can help in differentiating Möbius syndrome from perinatal trauma to peripheral nerves.
- In 2006, Cattaneo et al reported on a study of 24 Möbius syndrome patients after neurophysiologic testing including EMG and found 2 different defined phenotypes. Based on their EMG data, the authors postulated that the first group had rhombencephalic maldevelopment, while the second group seemed to have acquired a nervous system injury during intrauterine life.24
- In a 1996 study of EMG results from 7 patients with Möbius syndrome, Jaradeh et al suggested the primary cause of neural involvement was prenatal brainstem damage involving the motor nuclei and their internuclear connections.25
- The diagnosis of Möbius syndrome soon after birth may be difficult. Möbius syndrome can easily be confused with congenital myopathies or muscular dystrophies or congenital myotonic dystrophy. If abnormal, EMG findings can help in the differential diagnosis.
Histologic Findings
Few published cases contain pathologic descriptions.
Gross findings include asymmetry of the medulla, but the external appearance of the brain generally is normal.
Upon histologic evaluation, the most notable abnormalities have been seen in the motor nuclei of the cranial nerves, especially in CN VI (see Media File 2), CN VII, and CN XII and, to a lesser extent, in CN III and CN XI nuclei. CN VI often shows the most striking changes, with near-total neuronal loss and, sometimes, necrosis (see Media Files 3-4). The necrotic foci are round, well circumscribed, and basophilic. Degenerative periodic acid-Schiff–positive material may be seen.12 The necrotic foci may be surrounded by radiating cell processes.
Gliosis may be seen in the affected regions. Occasional axonal spheroids have been seen in the periphery of the necrotic lesions. The pyramids may appear underdeveloped. Atrophy of the facial muscles has been described, with adipose and fibrous tissue replacement.
Low-power photomicrograph of a brainstem specimen in an infant with Möbius syndrome who died at age 3 months. Image shows bilateral lesions in the pons of the abducens nuclei (hematoxylin and eosin stain).
Medium-power photomicrograph from the abducens nucleus in an infant with Möbius syndrome who died demonstrates diffuse necrosis and neuronal loss (hematoxylin and eosin stain).
High-power photomicrograph shows a lesion of an abducens nerve nucleus in an infant with Möbius syndrome who died at age 3 months. Image shows neuronal loss, necrosis, myxoid change, and a circumferential rim of thickened glial fibrils (hematoxylin and eosin stain).
More on Mobius Syndrome |
| Overview: Mobius Syndrome |
 Differential Diagnoses & Workup: Mobius Syndrome |
| Treatment & Medication: Mobius Syndrome |
| Follow-up: Mobius Syndrome |
| Multimedia: Mobius Syndrome |
| References |
| « Previous Page | Next Page » |
References
Von Graefe A, Saemisch T. Handbuch der gesammten Augenheilkunde. Leipzig, W Engelman. 1880;6:60.
Mobius PJ. Uber angeboren doppelseitige abducens-facialis-lahmung. Munchen Medizinische Wochenschrift. 1888;35:91-4.
Mobius PJ. Uber infantilen kernschwund. Munchen Medizinische Wochenschrift. 1892;39:17-21, 41-3, 55-8.
Henderson JL. The congenital facial diplegia syndrome: clinical features, pathology and etiology. Brain. 1939;62:381-403.
Verzijl HT, van der Zwaag B, Cruysberg JR, Padberg GW. Möbius syndrome redefined: a syndrome of rhombencephalic maldevelopment. Neurology. Aug 12 2003;61(3):327-33. [Medline].
Baraitser M. Genetics of Möbius syndrome. J Med Genet. Dec 1977;14(6):415-7. [Medline].
Strömland K, Sjögreen L, Miller M, Gillberg C, Wentz E, Johansson M, et al. Mobius sequence--a Swedish multidiscipline study. Eur J Paediatr Neurol. 2002;6(1):35-45. [Medline].
Kumar D. Moebius syndrome. J Med Genet. Feb 1990;27(2):122-6. [Medline].
Cohen SR, Thompson JW. Variants of Mobius' syndrome and central neurologic impairment. Lindeman procedure in children. Ann Otol Rhinol Laryngol. 1987;96(1 Pt 1):93-100. [Medline].
Verzijl HT, van Es N, Berger HJ, Padberg GW, van Spaendonck KP. Cognitive evaluation in adult patients with Möbius syndrome. J Neurol. Feb 2005;252(2):202-7. [Medline].
Gillberg C, Steffenburg S. Autistic behaviour in Moebius syndrome. Acta Paediatr Scand. Mar 1989;78(2):314-6. [Medline].
Towfighi J, Marks K, Palmer E, Vannucci R. Möbius syndrome. Neuropathologic observations. Acta Neuropathol (Berl). Oct 1979;48(1):11-7. [Medline].
Kanemoto N, Kanemoto K, Kamoda T, Hasegawa M, Arinami T. A case of Moebius syndrome presenting with congenital bilateral vocal cord paralysis. Eur J Pediatr. Aug 2007;166(8):831-3. [Medline].
Griz S, Cabral M, Azevedo G, Ventura L. Audiologic results in patients with Moebiüs sequence. Int J Pediatr Otorhinolaryngol. Sep 2007;71(9):1457-63. [Medline].
Sugarman GI, Stark HH. Mobius syndrome with Poland's anomaly. J Med Genet. 1973;10(2):192-6. [Medline].
Online Mendelian Inheritance in Man. %157900 - MOEBIUS SYNDROME; MBS. OMIM - Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=157900.
Ziter FA, Wiser WC, Robinson A. Three-generation pedigree of a Möbius syndrome variant with chromosome translocation. Arch Neurol. Jul 1977;34(7):437-42. [Medline].
Slee JJ, Smart RD, Viljoen DL. Deletion of chromosome 13 in Möbius syndrome. J Med Genet. Jun 1991;28(6):413-4. [Medline].
Kremer H, Kuyt LP, van den Helm B, van Reen M, Leunissen JA, Hamel BC, et al. Localization of a gene for Möbius syndrome to chromosome 3q by linkage analysis in a Dutch family. Hum Mol Genet. Sep 1996;5(9):1367-71. [Medline].
Nishikawa M, Ichiyama T, Hayashi T, Furukawa S. Mobius-like syndrome associated with a 1;2 chromosome translocation. Clin Genet. 1997;51(2):122-3. [Medline].
Pastuszak AL, Schüler L, Speck-Martins CE, Coelho KE, Cordello SM, Vargas F, et al. Use of misoprostol during pregnancy and Möbius' syndrome in infants. N Engl J Med. Jun 25 1998;338(26):1881-5. [Medline].
Puvabanditsin S, Garrow E, Augustin G, Titapiwatanakul R, Kuniyoshi KM. Poland-Möbius syndrome and cocaine abuse: a relook at vascular etiology. Pediatr Neurol. Apr 2005;32(4):285-7. [Medline].
Singh B, Shahwan SA, Singh P, al-Deeb SM, Sharif H. Mobius syndrome with basal ganglia calcification. Acta Neurol Scand. Jun 1992;85(6):436-8. [Medline].
Cattaneo L, Chierici E, Bianchi B, Sesenna E, Pavesi G. The localization of facial motor impairment in sporadic Möbius syndrome. Neurology. Jun 27 2006;66(12):1907-12. [Medline].
Jaradeh S, D'Cruz O, Howard JF Jr, Haberkamp TJ, Konkol RJ. Mobius syndrome: electrophysiologic studies in seven cases. Muscle Nerve. Sep 1996;19(9):1148-53. [Medline].
Briegel W. Neuropsychiatric findings of Mobius sequence -- a review. Clin Genet. Aug 2006;70(2):91-7. [Medline].
Carr MM, Ross DA, Zuker RM. Cranial nerve defects in congenital facial palsy. J Otolaryngol. Apr 1997;26(2):80-7. [Medline].
David TJ, Baumer JH. Problems of parental bonding and family care in child with the Möbius syndrome. J R Soc Med. Dec 1982;75(12):980-2. [Medline].
Dooley JM, Stewart WA, Hayden JD, Therrien A. Brainstem calcification in Möbius syndrome. Pediatr Neurol. Jan 2004;30(1):39-41. [Medline].
Johansson M, Wentz E, Fernell E, Strömland K, Miller MT, Gillberg C. Autistic spectrum disorders in Möbius sequence: a comprehensive study of 25 individuals. Dev Med Child Neurol. May 2001;43(5):338-45. [Medline].
Kuhn MJ, Clark HB, Morales A, Shekar PC. Group III Mobius syndrome: CT and MR findings. AJNR Am J Neuroradiol. 1990;11(5):903-4. [Medline].
Scarpelli AC, Vertchenko TB, Resende VL, Castilho LS, Paiva SM, Pordeus IA. Möbius syndrome: a case with oral involvement. Cleft Palate Craniofac J. May 2008;45(3):319-24. [Medline].
Smets K, Zecic A, Willems J. Ergotamine as a possible cause of Möbius sequence: additional clinical observation. J Child Neurol. May 2004;19(5):398. [Medline].
Further Reading
Keywords
congenital facial diplegia, congenital nuclear agenesis, congenital nuclear hypoplasia, congenital oculofacial paralysis, Möbius syndrome, loss of function of motor cranial nerves, Poland anomaly, congenital facial paralysis, Poland sequence
