Moebius Syndrome
Möbius Syndrome
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.
Presentation
Mobius syndrome (MS) is considered to be a rare disorder in clinical practice, with estimated incidence rates of 1 in 250,000 births [1]. The exact cause of this syndrome, as well as its pathogenesis, remain unknown, with current hypotheses involving genetic mutations and pathological events during embryogenesis [1] [2] [3] [4]. Although familial cases exist, most cases develop Mobius syndrome sporadically and the clinical presentation may be visible from neonatal period [1] [3]. The most important features of MS are palsies of the facial (VII) and abducens (VI) cranial nerves [1] [5]. 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 [1] [5]. 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) [1] [6]. Commonly reported findings are a fixed gaze, strabismus (either convergent or divergent), defects in abduction/adduction, and ptosis [1] [3] [6]. 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 [1] [3]. 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) [1] [3] [6] [7]. Finally, studies identified autism and mental retardation in up to a third of cases [5].
Entire Body System
Failure to Thrive in Infancy
- Additionally, the patient demonstrated failure to thrive during infancy and childhood, many dysmorphic features, lower limb anomalies, and hypogonadism in adulthood, but his intelligence was in the normal range.[ncbi.nlm.nih.gov]
Jaw & Teeth
Anterior Open Bite
- Potential to redevelop anterior open bites may likely be related to the functional deficiencies of the muscles of mastication and facial paralysis.[ncbi.nlm.nih.gov]
- This condition is called an anterior open bite and has facial/skeletal implications.[en.wikipedia.org]
Eyes
Strabismus
- 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]
Musculoskeletal
Hand Deformity
- 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]
Ears
Hearing Impairment
- 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
Mask-like Facies
- A case of Möbius' syndrome is presented, with the mask-like facies and poor social relationships consistent with this diagnosis. Previous thought has implicated the inability to transmit facial cues as a cause for impoverished social functioning.[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]
- The treatment of patients with Möbius syndrome is directed toward the restoration of motion secondary to the facial nerve palsy, which results in mask-like facies and inability to smile.[ajnr.org]
Short Neck
- 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]
Neurologic
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]
Screaming
- In the second season of Scream Queens, Daira Janessen ( Riley McKenna Weinstein ), also known as Chanel 8, has Möbius syndrome. In the first season of American medical drama The Good Doctor, a teenage patient is depicted with Möbius syndrome.[en.wikipedia.org]
Workup
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 [1] [8]. Calcifications of the brainstem have also been reported on computed tomography (CT) by isolated studies [9]. Despite the fact that certain genetic mutations have been revealed in patients with MS [1] [2] [4], specific genetic tests are yet to be designed.
Other Pathologies
Gliosis
- Postmortem examination revealed extensive bilateral brain gliosis and mineralization without evidence of inflammation, partial absence of cranial nerve nuclei III-XI, and a total absence of cranial nerve roots VI-XI.[ncbi.nlm.nih.gov]
Treatment
- From the WEST scientific·clinical From the EAST traditional·alternative There is no specific course of treatment for Moebius syndrome. Treatment is supportive and in accordance with symptoms.[goldbamboo.com]
- Subject(s) and methods: Twenty-nine patients with MS aged 0 to 4 underwent prospective dental examination as well as early orthodontic treatment.[ncbi.nlm.nih.gov]
Prognosis
- Patient: Moebius Syndrome Factsheet with description, pathogenesis, associated abnormalities, recognition, management and prognosis.[curlie.org]
- What is the prognosis? With close medical attention, the prognosis for most children with this condition is positive. Reviewed by: Saoussen Salhi, MD This page was last updated on: 4/23/2018 8:47:38 AM[nicklauschildrens.org]
- Prognosis Children may crawl and walk later. Most children with Moebius Syndrome eventually catch up. Speech problems often respond to therapy, but may persist due to impaired mobility of the tongue and/or mouth.[patient.info]
- Treatment and prognosis The disease is not progressive. Various plastic surgery procedures can be performed to attempt to recover facial muscles function. For example, microvascular transfer of a gracilis muscle to the face.[radiopaedia.org]
Etiology
- Although in many cases, evidence of an intrauterine vascular insult may be identified, a contributing genetic etiology should be considered, even in cases with strictly unilateral features.[ncbi.nlm.nih.gov]
Epidemiology
- Epidemiology In 2007, the Moebius Syndrome Foundation estimated that there were at the time a total of approximately 2,000 cases of Moebius Syndrome worldwide [6].[physio-pedia.com]
- Epidemiology [ edit ] It is estimated that there are, on average, 2 to 20 cases of Möbius syndrome per million births. [12] [13] Although its rarity often leads to late diagnosis, infants with this disorder can be identified at birth by a "mask-like"[en.wikipedia.org]
- Smith, Epidemiology of autism: Prevalence, associated characteristics, and implications for research and service delivery, Mental Retardation and Developmental Disabilities Research Reviews, 4, 2, (97-103), (1998).[doi.org]
Pathophysiology
- The pathophysiology of Möbius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome.[ncbi.nlm.nih.gov]
- Whatever the pathophysiology, our results suggest that the window of susceptibility for fetal development of Möbius' syndrome is wider than previously thought.[doi.org]
Prevention
- CONCLUSION(S): The early use of orthopedic appliances was important to prevent malocclusion and glossoptosis. Attempted abortion with misoprostol is associated with an increased risk of MS in infants.[ncbi.nlm.nih.gov]
- Prevention Moebius syndrome cannot be prevented as it is genetic. Treatment requires special care and monitoring by specialists. How is it diagnosed? At Medanta, the diagnosis is made on the basis of symptoms described by the patient.[medanta.org]
- Primary prevention Since it's a genetic disorder, not much can be done about prevention, but early screening of all neonates is required.[eyewiki.aao.org]
- When a tooth is lost prematurely, removable or fixed spacers may be needed to prevent the shifting of teeth.[en.wikipedia.org]
- Traditionally both superior and inferior rectus transposition are done to prevent any post operative vertical imbalance.[nepjol.info]
References
Article
- 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.