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Möbius’ sequence

Rare non-progressive disorder defined by bilateral congenital paralysis of the 6th and 7th cranial nerves in combination with various odontological, craniofacial, ophthalmological and orthopaedic conditions.

Rare non-progressive disorder defined by bilateral congenital paralysis of the 6th and 7th cranial nerves in combination with various odontological, craniofacial, ophthalmological and orthopaedic conditions.

Congenital cranial dysinnervation disorders (CCDD):

Primary/secondary muscle dysinnervation disorders arising from congenital developmental anomalies or complete absence of one or multiple cranial nerves
  • Duane retraction anomaly
  • Congenital fibrosis of extraocular muscles (CFEOM)
  • Horizontal gaze palsy
  • Congenital ptosis
  • Congenital facial palsy
  • Möbius’ sequence

History:

Moebius syndrome is a congenital facial weakness combined with abnormal ocular abduction in most studies. In 1888, a German neurologist, Paul Julius Mobius, first described the clinical entity of Mobius syndrome. He reported patients with congenital and delayed facial and abducent nerve palsy. However, von Graaefe was the first to report patients with facial diplegias. Hallmarks of Mobius syndrome mainly consist of paresis of 6th and 7th nerves. It may or may not be associated with paralysis of other cranial nerves (III, V, VI, IX, X) and abnormalities of the limb (syndactyly, brachydactyly or absence of digits), chest wall, spine and soft tissues.

Aetiology

Aetiology of the syndrome still remains unknown, and most cases reported are sporadic.

  • Maternal drug exposure: Misoprostol, thalidomide, cocaine, alcohol, benzodiazepines, ergotamine

Pathophysiology

Several features associated with Moebius syndrome are considered to derive from abnormal development of the rhombencephalon (hindbrain), which develops into the medulla, pons, and cerebellum. Although the pathogenesis remains unknown, an intrauterine vascular event linked to subclavian artery disruption or a toxic injury in the critical period during the first trimester has been proposed.

Clinical features

Broad spectrum of symptoms and signs in the cranio-maxillofacial region.

Complete/incomplete unilateral/bilateral facial paralysis associated with bilateral abducens nerve palsy:

Non-progressive, congenital, unilateral or bilateral palsy of the 6th and 7th cranial nerves
  • Incomplete closure of eyelid during sleep
  • Drooling of saliva from the mouth
  • Difficulty in sucking
  • Masklike facies: Lack of facial movement when crying, inability to smile
  • Asymmetry of angles of mouth
  • Indistinct speech secondary to the inability to close the lips, leading to labial sound
Convergent strabismus and right facial palsy, dysmorphic facial appearance | Albayrak, H. M., Tarakçı, N., Altunhan, H., Örs, R., & Çaksen, H. (2017). A congenital cranial dysinnervation disorder: Möbius’ syndrome. Turk pediatri arsivi, 52(3), 165–168. https://doi.org/10.5152/TurkPediatriArs.2017.2931

Musculoskeletal deformities:

  • Primary motor problems: Hypotonia, musculo-skeletal dysmorphism, delay in righting, locomotion and clumsiness.
  • Limb abnormalities: Lower extremity truncating defects, oligodactyly, syndactyly, and/or talipes equinovarus
  • Klippel Feil syndrome (KFS): Abnormal fusion of ≥ 2 cervical vertebrae
  • Poland anomaly: Ipsilateral aplasia/hypoplasia of the pectoralis muscle plus hand and digit anomalies
Hands and arm deformities of two patients with Moebius. Clinical photographs and radiographs of the hand and arm of patient no. 1 (a-d) shows terminal transverse congenital deficiency of the right forearm with a radioulnar synostosis, brachydactyly (shortness of fingers) of the five fingers on the left hand, slight syndactyly of the left second and third finger and camptodactyly (flexion contracture of the proximal interphalangeal joints) of the left fourth and fifth finger. Clinical photographs and radiographs of the hands of patient no. 3 (e-h) shows brachydacyly of all ten fingers, slight syndactyly of the left second and third finger, adactyly of the left second finger and camptodactyly of the right fourth and fifth finger | Pedersen, L. K., Maimburg, R. D., Hertz, J. M., Gjørup, H., Pedersen, T. K., Møller-Madsen, B., & Østergaard, J. R. (2017). Moebius sequence -a multidisciplinary clinical approach. Orphanet journal of rare diseases, 12(1), 4. https://doi.org/10.1186/s13023-016-0559-z

Orofacial dysmorphism:

  • Feeding disorders: Sucking-swallowing difficulty, breathing problems, lack of the sensitivity of the orofacial area, dysphagia with the need, in severe cases, for a gastrostomy
  • Facial malformations: Depressed nasal bridge, anteverted nostrils, thin upper lip, downturned mouth corners, bilateral epicanthus, and micrognathia
  • Language difficulties: Dyslalia, mechanical disorders of phonological coding and speech structure and writing were common.
  • Visual impairment: Scanning, exploration and visual-perceptual deficits, and, in some cases, corneal ulcers.
Clinical photograph showing club foot (A). Image shows convex profile, hypoplastic mandible (B). Shows inability to close eyes (C). Clinical photograph shows low set ears, impaired facial expressions and absence of forehead wrinkling and torticollis (D). | Ghosh, R., Shetty, V., Hegde, S., Babu, G. S., Ajila, V., Kishore P, N., & Nair, M. (2017). Rare features associated with Mobius syndrome: Report of two cases. Journal of dental research, dental clinics, dental prospects, 11(1), 60–65. https://doi.org/10.15171/joddd.2017.012

CNS finings:

  • Cognitive retardation
  • Epilepsy

Diagnosis

International Classification of functioning Children and Youth (ICF-CY) framework:

GOLD STANDARD framework for interpreting functions (vs impairment), activities (vs disability) and participation (vs handicap), in children with MBS and for evaluation and intervention of the familial and social environment
MBS’ Interpretation ICF | Picciolini, O., Porro, M., Cattaneo, E., Castelletti, S., Masera, G., Mosca, F., & Bedeschi, M. F. (2016). Moebius syndrome: clinical features, diagnosis, management and early intervention. Italian journal of pediatrics, 42(1), 56. https://doi.org/10.1186/s13052-016-0256-5

Radiography:

In accordance with affected regions
Panoramic view showing decayed tooth with respect to maxillary left second premolar, first molar and mandibular right and left first molar (A). Hand wrist radiograph showing short middle phalanges in the index finger of both hands (B and C). Lateral cephalogram shows no abnormality (D). | Ghosh, R., Shetty, V., Hegde, S., Babu, G. S., Ajila, V., Kishore P, N., & Nair, M. (2017). Rare features associated with Mobius syndrome: Report of two cases. Journal of dental research, dental clinics, dental prospects, 11(1), 60–65. https://doi.org/10.15171/joddd.2017.012

MRI (brain):

  • Agenesis of corpus callosum, absent septum pellucidum, hypoplastic olfactory nerves, mild brainstem hypoplasia, and simplified gyral patterns
  • Hypoplastic vertebral arteries

Differential diagnosis:

  • Melkersson-Rosenthal syndrome
  • Congenital facial muscular atrophy
  • Muscular dystrophy
  • Cerebral palsy
  • Congenital myopathies

Management

Definitive medical treatment is not available for Mobius syndrome, therefore, medical care is only supportive and symptomatic. Parental education plays a major role in the patient’s life.

Surgical management:

Restoration of motion secondary to the facial nerve palsy that results in mask-like facies and inability to smile is the prime aim of the treatment plan.
  • Plastic surgery reconstruction with muscle transplantation (ideally at an early age)
  • Ocular surgeries
  • Orthognathic surgeries
  • Surgical corrections for other associated abnormalities
The frontal facial view of two females with Moebius, maximal lip-closure. Patient no. 5 (a) have poor facial expression and was only able to force the lower lip into contact with the upper incisors, but the labial surfaces of the upper incisors remained partly uncovered. Patient no. 4 (b) have had “smile surgery” performed seen as indentations on the cheeks but was not able to close the lips | Pedersen, L. K., Maimburg, R. D., Hertz, J. M., Gjørup, H., Pedersen, T. K., Møller-Madsen, B., & Østergaard, J. R. (2017). Moebius sequence -a multidisciplinary clinical approach. Orphanet journal of rare diseases, 12(1), 4. https://doi.org/10.1186/s13023-016-0559-z

Other intervention programs:

  • Physical therapy (for congenital orthopedic problems)
  • Occupational therapy (help with daily activities)
  • Speech therapy (for severe facial nerve paralysis)

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