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].

• Epilepsy

  Epilepsy, mental retardation and autism may be present. [eye.com.ph]

  The authors suggested that the cocaine exposure may have disrupted the fetal vascular supply. [20] Kanemoto reported on the mother of an infant with Möbius syndrome who was treated with zonisamide during pregnancy for prepartum epilepsy. [emedicine.com]

  Biology of Juvenile Myoclonic Epilepsy The investigators are collecting genetic information through blood samples as well as clinical and EEG data from over 1000 people with Juvenile Myoclonic Epilepsy (JME) across the UK, Europe and North America. [icahn.mssm.edu]

• Ulcer

  Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. [ncbi.nlm.nih.gov]

  Abstract Canadian Family Physician May 2001, 47 (5) 951-953; Abstract QUESTION: I prescribed misoprostol to one of my patients with a peptic ulcer. [cfp.ca]

  In a 1998 study of Brazilian infants, Pastuszak et al found a strong association between Möbius syndrome and prenatal use of misoprostol, a synthetic prostaglandin analog used to treat upper gastrointestinal ulceration. [18] Misoprostol was self-administered [emedicine.com]

• 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]

  It makes me smile ear to ear every time I hear it. "Our journey would be so much harder if he didn't have such a hearty, wonderful laugh." 'WHY WOULD SOMEONE DO THIS TO ME?' [thesun.co.uk]

• Hand Deformity

  Claw hand Claw hand 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]

  Club foot deformities will need to be corrected by an orthopedic surgeon. Hand deformities are most often characterized by an underdeveloped hand (or, symbrachydactyly). [drpanossian.com]

  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]

• 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]

  Clinical History A 14-year-old female presented permanent convergent strabismus and absence of facial mimic in the neurological evaluation. [eurorad.org]

  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]

  Taylor, Strabismus/ Fibrosis syndromes, 47 Pan-Hellenic Congress of ophthalmology, Thessaloniki, Northern Greece Society of Ophthalmology, 2014 [eyewiki.aao.org]

• Suggestibility

  Both reports suggested that a gene responsible for Möbius syndrome is located in region 13q12.2-q13. [emedicine.com]

  We demonstrated three distinct patterns of abnormalities suggesting different sites of the primary lesion in different patients. [ncbi.nlm.nih.gov]

• Mask-like Facies

  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]

  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]

  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]

• 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 features were shortness of the neck associated with torticollis. [doi.org]

• Forgetful

  Don't forget to link back here so that others can join in the fun! [iamthedivaczt.blogspot.com]

  However, friends and family who are familiar with the person with Moebius syndrome learn to recognize other signals of emotion such as body language, and they sometimes report forgetting that the person has facial paralysis altogether. [moebiussyndrome.info]

  Don't forget books, videos, and websites. The listing below will get you started. FACES: The National Craniofacial Association P. O. [faces-cranio.org]

  Never forget or deny your own uniqueness, individuality and utter beauty. When you value and love yourself, it shows. I’m not too sure who said this, but I think it’s a beautiful quote and one which really inspires me. [manyfacesofmoebiussyndrome.com]

• 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]

  The most common cranial nerve involved is the 6th cranial nerve (abducent). The oculomotor and trochlear can also be involved. [annsaudimed.net]

  Results Involvement of the VII cranial nerve (total/partial, bilateral or unilateral) was present in 96 % of patients, and of the VI nerve in 85 %. [ijponline.biomedcentral.com]

• Facial Muscle Weakness

  Abnormal development of cranial nerves leads to the facial muscle weakness or paralysis that is characteristic of Moebius syndrome. [medlineplus.gov]

  An issue with development of cranial nerves leads to facial muscle weakness or paralysis, something that is characteristic of Moebius syndrome. [disabled-world.com]

• Perseveration

  Taylor is a humorous and stubborn figure, full of hope and perseverance. [amazon.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 [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.

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]

This surgical treatment resulted in marked improvement of said deficits. [J Pediatr Ophthalmol Strabismus. 2017;54:e81-e82.]. [ncbi.nlm.nih.gov]

Read More Read Less Treatment Treatment There is no specific course of treatment for Moebius syndrome. Treatment is supportive and in accordance with symptoms. Infants may require feeding tubes or special bottles to maintain sufficient nutrition. [ninds.nih.gov]

Read PDF Candidates for Moebius Syndrome Treatment Moebius syndrome treatment is usually performed on children before they enter school. [facialparalysisinstitute.com]

Patient: Moebius Syndrome Factsheet with description, pathogenesis, associated abnormalities, recognition, management and prognosis. [curlie.org]

Read More Read Less Prognosis Prognosis There is no cure for Moebius syndrome. In spite of the impairments that characterize the disorder, proper care and treatment give many individuals a normal life expectancy. Clinical Trials Clinical Trials [ninds.nih.gov]

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]

[…] ventriculomegaly without obstructive hydrocephalus, especially frontal horn prominence corpus callosum dysplasia hippocampal malrotation cerebellar hypoplasia, especially vermian hypoplasia cerebral aqueduct stenosis with hydrocephalus Treatment and prognosis [radiopaedia.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]

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]

Etiology is multifactorial, and several theories have been proposed, with the most supported theory being of a transient ischemic or hypoxic insult to the fetus. Infectious and genetic etiologies have also been proposed. [radiopaedia.org]

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]

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]

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]

Epidemiology Mobius syndrome is a rare disorder. Only approximately 300 cases have been described in the English-language literature. [emedicine.medscape.com]

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]

Pathophysiology: The complete pathophysiological description of Möbius syndrome remains elusive. Whether nerve, brainstem, or muscle aplasia is the primary event has not been established. [baillement.com]

A great deal of useful information, as well as support group information, is available on the Web site. [10] Pathophysiology Numerous theories exist concerning the primary underlying pathogenesis of Möbius syndrome. [emedicine.medscape.com]

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]

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]

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]

Furthermore, the possibility to investigate a larger number of cases expands the opportunity to better characterize clinical conditions, methods of assessment, prognosis, and prevention program development, as well as health promotion of individuals diagnosed [arquivosdeorl.org.br]

Prevention How can I prevent Moebius syndrome? There is no way to prevent Moebius syndrome. Scientists are still working to understand what causes it and possible risk factors. [my.clevelandclinic.org]

1. Picciolini O, Porro M, Cattaneo E, et al. Moebius syndrome: clinical features, diagnosis, management and early intervention. Ital J Pediatr. 2016;42:56.
2. 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.
3. Kumar D. Moebius syndrome. J Med Genet. 1990;27(2):122-126.
4. 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.
5. Strömland K, Sjögreen L, Miller M, et al. Mobius sequence--a Swedish multidiscipline study. Eur J Paediatr Neurol. 2002;6(1):35-45.
6. 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.
7. Abramson DL, Cohen MM Jr, Mulliken JB. Möbius syndrome: classification and grading system. Plast Reconstr Surg. 1998;102(4):961-967.
8. 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.
9. Dooley JM, Stewart WA, Hayden JD, Therrien A. Brainstem calcification in Möbius syndrome. Pediatr Neurol. 2004;30(1):39-41.