The challenging management of Moebius syndrome using orthodontic camouflage: A case report.

Moebius syndrome (MS) is a rare congenital neuromuscular disorder characterized by weakness or paralysis (palsy) of abducens and facial nerves, or other cranial nerves which may be affected. Diagnosis, treatment, and dental management of MS patients are focused on treating manifestations like malocclusion, while catering to associated extraoral (neurologic, dermatologic, ocular) complications, aiming to improve their quality of life. Here, we report the case of a 9-year-old female patient with MS who underwent orthodontic camouflage using combined orthopedic-orthodontic therapy using a high-pull chin cup and fixed orthodontic appliance to improve skeletal mal-relation and facial appearance. The outcome displayed great improvement in function and better esthetics, improving not only the patient's but also the family's quality of life. A year's follow-up showed successful maintenance of the achieved results. A multidisciplinary approach in MS not only helps in overcoming the treatment challenges but also provides great psychosocial benefits to these patients.

Inability to move one's face dampens facial expression perception.

Humans rely heavily on facial expressions for social communication to convey their thoughts and emotions and to understand them in others. One prominent but controversial view is that humans learn to recognize the significance of facial expressions by mimicking the expressions of others. This view predicts that an inability to make facial expressions (e.g., facial paralysis) would result in reduced perceptual sensitivity to others' facial expressions. To test this hypothesis, we developed a diverse battery of sensitive emotion recognition tasks to characterize expression perception in individuals with Moebius Syndrome (MBS), a congenital neurological disorder that causes facial palsy. Using computer-based detection tasks we systematically assessed expression perception thresholds for static and dynamic face and body expressions. We found that while MBS individuals were able to perform challenging perceptual control tasks and body expression tasks, they were less efficient at extracting emotion from facial expressions, compared to matched controls. Exploratory analyses of fMRI data from a small group of MBS participants suggested potentially reduced engagement of the amygdala in MBS participants during expression processing relative to matched controls. Collectively, these results suggest a role for facial mimicry and consequent facial feedback and motor experience in the perception of others' facial expressions.

Síndrome de Moebius y ortotropía en posición primaria: ¿es infrecuente esta asociación? (Colombia) / Moebius syndrome and orthotropia in primary position: is this association uncommon? (Colombia) / Síndrome de Moebius e ortotropia em posição primária: é uma associação incomum? (Colômbia)

El síndrome de Moebius es una enfermedad congénita poco común que se caracteriza por el compromiso unilateral o bilateral del VI y VII par craneal, lo que compromete los músculos que controlan la oculomotricidad, produciendo una parálisis en la abducción del globo ocular y los músculos involucrados en la expresión facial. Su presentación clínica y grados de severidad son variables, puede presentar compromiso simétrico o asimétrico. Adicionalmente, gran parte de los casos se relacionan con trastornos del lenguaje, anomalías musculoesqueléticas y orofaciales. En el presente artículo se presenta el caso de una paciente femenina de 3 años producto de un embarazo trigemelar con diagnóstico clínico de síndrome de Moebius al nacer, confirmado por neuroimagen en la que se evidencia la ausencia bilateral del nervio facial en ángulos pontocerebelosos, adicionalmente con un defecto completo en los movimientos oculares de abducción y aducción lo que impide el estrabismo convergente común en estos pacientes.

Moebius syndrome is a rare congenital disease characterized by unilateral or bilateral involvement of the VI and VII cranial nerves, which compromises the muscles that control ocular motricity with paralysis in the abduction of the eyeball and the muscles involved in the facial expression. Its clinical presentation and degrees of severity are variable, and it can be symmetric or asymmetric. Additionally, most of the cases are related to language disorders, musculoskeletal and orofacial anomalies. This paper presents the case of a 3-year-old female patient, product of a trigemellar pregnancy with a clinical diagnosis of Moebius syndrome at birth, confirmed by neuroimaging, which shows the bilateral absence of the facial nerve in point-lateral angles. Additionally she has a complete defect in abduction and adduction eye movements, which prevents the common convergent strabismus in these patients.

A síndrome de Moebius é uma doença congênita rara caracterizada pelo envolvimento unilateral ou bilateral dos nervos cranianos VI e VII, que compromete os músculos que controlam a oculomotricidade com paralisia na abdução do globo ocular e dos músculos envolvidos na expressão facial. Sua apresentação clínica e graus de gravidade são variáveis, podendo ser um comprometimento simétrico ou assimétrico. Além disso, a maioria dos casos está relacionada a distúrbios de linguagem, anomalias musculoesqueléticas e orofaciais. Este paper apresenta o caso de uma paciente de 3 anos de idade, fruto de uma gravidez trigêmea com diagnóstico clínico de Síndrome de Moebius ao nascimento, confirmado por neuroimagem em que é evidente a ausência bilateral do nervo facial nos ângulos ponto-cerebelares. Além disso, ela tem um defeito completo nos movimentos oculares de abdução e adução, o que impede o estrabismo convergente comum nesses pacientes.

Poland-Möbius syndrome: a case report implicating a novel mutation of the PLXND1 gene and literature review.

BACKGROUND: Möbius (Moebius) and Poland's syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6th and 7th cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors. The PLXND1 gene codes for a protein expressed in the fetal central nervous system and vascular endothelium and is thus involved in embryonic neurogenesis and vasculogenesis. It is located at chromosome region 3q21-q22, a locus of interest for Möbius syndrome. CASE PRESENTATION: We present the first report of a patient with Poland-Möbius syndrome and a mutation in the PLXND1 gene. A child with Poland-Möbius syndrome and a maternally inherited missense variant (NM_015103.2:ex14:c.2890G > Ap.V964M) in the PLXND1 gene is described. In order to contextualize these findings, the literature was examined to identify other confirmed cases of Poland-Möbius syndrome for which genetic data were available. Fourteen additional cases of Poland-Möbius syndrome with genetic studies are described in the literature. None implicated the PLXND1 gene which has previously been implicated in isolated Möbius syndrome. CONCLUSIONS: This report provides further evidence in support of a role for PLXND1 mutations in Möbius syndrome and reasserts the nosological link between Möbius and Poland's syndromes. LEVEL OF EVIDENCE: Level V, Descriptive Study.

Difficult intubation and postoperative aspiration pneumonia associated with Moebius syndrome: a case report.

BACKGROUND: Moebius syndrome is a rare congenital disorder characterized by non-progressive palsy of the abducens (VI) and facial (VII) cranial nerves. Its common features include dysfunctions associated with other cranial nerves, orofacial abnormalities, skeletal muscle hypotonia, and other systemic disorders of differing severities. There are several concerns in the perioperative management of patients with Moebius syndrome. CASE PRESENTATION: We present a report on the management of general anesthesia of a 14-year-old male patient with Moebius syndrome who was scheduled for mandibular cystectomy. The patient was diagnosed with Moebius syndrome at the age of 7 years based on his clinical manifestations of nerve palsy since birth and cranial nerve palsy of the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and sublingual nerves (XII). The patient's oral morphological abnormalities made intubation difficult. He also experienced dysphagia and aspiration pneumonia on a daily basis. Oral secretions were frequently suctioned postoperatively. However, after discharge, the patient developed aspiration pneumonia and was readmitted to the hospital. CONCLUSIONS: The main problem arising when administering general anesthesia to patients with this syndrome is difficult airway management. The oral abnormalities in these patients, such as small jaw and extreme dental stenosis, make mask ventilation and intubation difficult. Furthermore, this syndrome often involves respiratory impairment and dysphagia due to cerebral nerve palsy, so there is a high risk of postoperative respiratory complications. Since multiple organs are affected in patients with Moebius syndrome, appropriate perioperative management strategies must be prepared for these patients.

Degenerate pathway for processing smile and other emotional expressions in congenital facial palsy: an hdEEG investigation.

Influential theoretical models argue that an internal simulation mechanism (motor or sensorimotor simulation) supports the recognition of facial expressions. However, despite numerous converging sources of evidence, recent studies testing patients with congenital facial palsy (i.e. Moebius syndrome) seem to refute these theoretical models. However, these results do not consider the principles of neuroplasticity and degeneracy that could support the involvement of an alternative neural processing pathway in these patients. In the present study, we tested healthy participants and participants with Moebius syndrome in a highly sensitive facial expression discrimination task and concomitant high-density electroencephalographic recording. The results, both at the scalp and source levels, indicate the activation of two different pathways of facial expression processing in healthy participants and participants with Moebius syndrome, compatible, respectively, with a dorsal pathway that includes premotor areas and a ventral pathway. Therefore, these results support the reactivation of sensorimotor representations of facial expressions (i.e. simulation) in healthy subjects, in the place of an alternative processing pathway in subjects with congenital facial palsy. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

Neurogenic bladder as a lurking complication in Moebius syndrome.

Moebius syndrome (MBS) is a congenital disorder characterized by facial and abducens palsy, sometimes accompanied with other cranial nerve palsies and comorbid conditions. Anatomical anomalies of the brainstem are assumed to be major etiologies of MBS. Its phenotypic presentation can be variable. We report a female patient with MBS who presented with neurogenic bladder (NB). She was born via normal vaginal delivery. At birth, she showed bilateral abducens palsy and right facial palsy. We diagnosed MBS by cranial computed tomography scan and magnetic resonance imaging. She had recurrent urinary tract infection. Hydronephrosis was noted on ultrasonography and bilateral vesicoureteral reflux (grade 5) on voiding cystourethrography. Urodynamic investigation showed detrusor overactivity and detrusor-sphincter dyssynergia, which follow the pattern of NB resulting from infrapontine-suprasacral lesions. Patients with MBS have lower brainstem dysfunction, and accordingly we should be aware of NB.

Prevalence of Hand Malformations in Patients With Moebius Syndrome and Their Management.

BACKGROUND: Moebius syndrome is a disorder characterized by facial and abducens nerve paralysis. Patients can present a wide range of upper extremity malformations. Literature focused on orthopedic manifestations of Moebius syndrome shows variability in the prevalence and clinical presentation of upper extremity anomalies. The aim of this work is to evaluate the prevalence of upper extremity malformations in patients with Moebius syndrome, clarify its various clinical presentations, and present treatment strategies for their management. METHODS: This is a retrospective, cross-sectional study including patients with Moebius syndrome and upper extremity malformations between 2012 and 2019. Data include demographic characteristics, Moebius syndrome subtype, type of malformation, affected extremity, and surgical procedures underwent. Quantitative data were recorded as mean (standard deviation [SD]), and qualitative data were expressed in terms of totals and percentages. Statistical association between Moebius syndrome subtype and development of upper extremity anomalies was evaluated using binary logistic regression. RESULTS: Twenty-five out of 153 patients (16.3%) presented upper extremity malformations (48% male). Mean age of presentation was 9.08 ± 9.43 years. Sixty-eight percent of the malformations were unilateral. The most common presentations included Poland syndrome and simple syndactyly with 8 cases each (32%), followed by 5 cases of brachysyndactyly (20%), 3 cases of amniotic band syndrome (12%), and 1 case of cleft hand (4%). No statistical association was found between Moebius syndrome subtype and odds ratio for development of upper extremity anomalies. Thirteen patients (52%) underwent reconstructive procedures. CONCLUSION: Poland syndrome and syndactyly are the most common anomalies in patients with Moebius syndrome. Patients may present with a wide range of hand malformations, each patient should be carefully evaluated in order to determine whether surgical treatment is needed and to optimize rehabilitation protocols.

Diagnosis and treatment of speech disorders in children with Moebius syndrome.

BACKGROUND: Moebius syndrome (MS) is characterized by congenital bilateral paralysis of the facial and abducens nerves. Clinical features include feeding problems, dysarthria, dysphagia, sialorrhea, strabismus, and lack of facial expression. Patients with MS frequently present with dysphagia during infancy. Further on during childhood a severe speech disorder is a common feature. However, articulation deficits in patients with MS are scarcely reported in the related scientific literature. OBJECTIVE: The aim of this study is to describe speech deviations, intelligibility and sialorrhea in patients with MS. MATERIAL AND METHODS: Eighty-seven patients with MS were prospectively studied. Age ranged from 4 to 18 years. A complete Speech and Language Pathology (SLP) evaluation was performed in all cases. The evaluation focused on articulation placement, sialorrhea and intelligibility of speech. RESULTS: Sialorrhea was detected in 23% of the patients. Abnormal articulation placement of bilabial phonemes was observed in 68% of the patients. Another 50% of the patients presented with articulation placement errors in other phonemes. Intelligibility was classified as adequate in 18% of the cases. Mildly affected intelligibility was found in 51% of the patients. Speech was considered moderately unintelligible in 20% of the cases. Unintelligible speech was found in 11% of the patients. CONCLUSIONS: From the results of this prospective study it can be concluded that a high percentage of patients with MS are at high risk of presenting with moderate to severe speech disorders. Thus, an early SLP intervention should be provided for this population in order to enhance speech development and reducing the risk of severe oral communication impairments.

Etiology of Childhood Bilateral Sensorineural Hearing Loss in Shandong Province, China.

Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for those children who were identified as having hearing loss to identify the potential cause. Results The etiology of bilateral SNHL in our sample was genetic in 874 (39.3%), acquired in 650 (29.3%), and unknown in 697 (31.4%) children. Among children with acquired SNHL, the cause was maternal viral infection in 75 (11.5%); perinatal factors in 238 (36.6%); meningitis, measles, and mumps in 146 (22.5%); and ototoxic exposure in 117 (18%) children. Among the children with genetic SNHL, only 44 (4.9%) were identified as having syndromic hearing loss, and the remainder (95.1%) were classified as nonsyndromic hearing loss. Conclusion The findings indicated that nearly 30% of bilateral SNHL in Shandong province could be preventable through immunization, early prenatal diagnosis, proper treatment of infections, and avoidance of prescription of ototoxic drugs. This finding emphasizes the need for programs aimed at improving the health services at primary and secondary levels of health care, which will in turn prevent childhood hearing loss.

Associated syndromes in patients with Pierre Robin Sequence.

OBJECTIVES: Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current literature reports that Stickler syndrome is the most common syndrome associated with PRS, and 22q11 deletion syndrome (22q11 DS) as the second most common. This study identifies associations between PRS and genetic syndromes. METHODS: A retrospective chart review was performed to identify patients diagnosed with PRS over a 10-year period from 4/1/2007 to 4/1/2017 at a tertiary children's hospital. RESULTS: 4,052 consecutive charts were reviewed and 234 patients had a diagnosis of PRS confirmed with the triad of micrognathia, glossoptosis, and airway obstruction. Of note, all of these patients had cleft palate. Of the 234 patients with PRS, 65 patients had syndromic diagnoses (28%). One patient had 22q11 DS (0.43%), and 31 patients had Stickler syndrome (13.2%). Additionally, 3 patients had central hypoventilation syndrome, 3 patients had Duane syndrome, 2 patients had Cornelia de Lange syndrome, 2 patients had Emanuel syndrome, 2 patients had Gordon syndrome, 2 patients had Mobius syndrome, 2 patients had Nager syndrome. Multiple other syndromes were identified, but occurred in isolated cases. CONCLUSION: This study supports literature that PRS is most commonly associated with Stickler Syndrome but rarely associated with 22q11 DS given that only 1 patient had both PRS and 22q11 DS.

Difficult Airway Identification and Management in Patients With Moebius Syndrome.

BACKGROUND: Airway management in patients with Moebius syndrome can be difficult due to the presence of orofacial malformations. This paper aims to present our institution's experience in the evaluation and management of the upper airway in patients with Moebius syndrome METHODOLOGY:: The authors performed a retrospective study including every patient with Moebius syndrome submitted to surgery between 2012 and 2017. Difficult airway was defined as one requiring more than 2 attempts to achieve endotracheal tube placement, a Mallampati score equal or above III, a Cormack score equal or above III, or need of a fiberscope during intubation. RESULTS: Fifty-one patients were included, (39.3% males) requiring 172 procedures. Each patient required an average of 3.37 ±â€Š1.94 anesthetic events. Average Body Mass Index (BMI) was 20.07 ±â€Š6.06, 45.1% were overweight or obese. Four patients (7%) were considered as having a potentially difficult airway. Endotracheal intubation was achieved in all patients; 38 patients were intubated in a single attempt, while the rest were successfully intubated on a second try. Fiberscope was not necessary. Univariate analysis showed that overweight/obese patients were more likely to be considered as having a difficult airway (P = 0.03). CONCLUSION: Intubation can be difficult in patients with Moebius syndrome, but failure is rare. Overweight or obese patients are at risk of presenting a difficult airway. An extensive preoperative evaluation and adequate communication between the members of the multidisciplinary team in charge of these patients is paramount.

Mobius syndrome and obsessive compulsive disorder: a case report.

BACKGROUND: Mobius syndrome is characterized by a bilateral congenital paralysis of the facial and abducens nerves which leaves the subject with an expressionless "mask-like" face. SUBJECTS AND METHODS: Based on a literature review and a case discussion of an adult patient with Mobius syndrome and obsessive-compulsive disorder, initially undiagnosed and confused with a psychotic disorder, we will discuss the influence of Mobius syndrome in psychiatric evaluations. RESULTS: The lack of facial expressiveness and non-verbal emotional interactions may influence psychiatric evaluations and result in misdiagnosis and the inappropriate prescribing of antipsychotics. In the case analysis, we also observed other associated malformations such as renal atrophy, a bicuspid aortic valve and mitral valve prolapse. CONCLUSION: We feel that educating the patient about the communicative consequences of impaired facial expressions and facial interactions is a necessary prerequisite for any psychiatric or psychological evaluation in subjects with Mobius syndrome. We also recommend using caution when prescribing antipsychotics in patients with Mobius syndrome given the motor side effects secondary to a potentially pre-existing hypotonia.

Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing.

BACKGROUND: Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others' facial expressions? METHODS: We investigated whether psychophysiological emotional responses to others' facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others' social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). RESULTS: There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. CONCLUSION: Results support "embodied" theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation.

Divergent roles of Plexin D1 in cancer.

Plexin D1 belongs to a family of transmembrane proteins called plexins. It was characterized as a receptor for semaphorins and is known to be essential for axonal guidance and vascular patterning. Mutations in Plexin D1 have been implicated in pathologic conditions such as truncus arteriosus and Möbius syndrome. Emerging data show that expression of Plexin D1 is deregulated in several cancers; it can support tumor development by aiding in tumor metastasis and EMT; and conversely, it can act as a dependence receptor and stimulate cell death in the absence of its canonical ligand, semaphorin 3E. The role of Plexin D1 in tumor development and progression is thereby garnering research interest for its potential as a biomarker and as a therapeutic target. In this review, we describe its discovery, structure, mutations, role(s) in cancer, and therapeutic potential.

Autonomic Responses to Emotional Stimuli in Children Affected by Facial Palsy: The Case of Moebius Syndrome.

According to embodied simulation theories, others' emotions are recognized by the unconscious mimicking of observed facial expressions, which requires the implicit activation of the motor programs that produce a specific expression. Motor responses performed during the expression of a given emotion are hypothesized to be directly linked to autonomic responses associated with that emotional behavior. We tested this hypothesis in 9 children (M age = 5.66) affected by Moebius syndrome (MBS) and 15 control children (M age = 6.6). MBS is a neurological congenital disorder characterized by underdevelopment of the VI and VII cranial nerves, which results in paralysis of the face. Moebius patients' inability to produce facial expressions impairs their capacity to communicate emotions through the face. We therefore assessed Moebius children's autonomic response to emotional stimuli (video cartoons) by means of functional infrared thermal (fIRT) imaging. Patients showed weaker temperature changes compared to controls, suggesting impaired autonomic activity. They also showed difficulties in recognizing facial emotions from static illustrations. These findings reveal that the impairment of facial movement attenuates the intensity of emotional experience, probably through the diminished activation of autonomic responses associated with emotional stimuli. The current study is the first to investigate emotional responses in MBS children, providing important insights into the role of facial expressions in emotional processing during early development.

Characterization of Hand Anomalies Associated With Möbius Syndrome.

PURPOSE: To investigate the distinguishing morphological characteristics of the upper extremities in children with Möbius syndrome. METHODS: Twenty-seven involved extremities in 14 patients with a diagnosis of Möbius syndrome were identified at 2 institutions. Medical records, radiographs, and clinical photographs were evaluated. Congenital hand differences were classified according to the Oberg, Manske, and Tonkin classification, and hands with symbrachydactyly were classified by the Blauth and Gekeler classification. The presence of other congenital anomalies was catalogued. RESULTS: There was bilateral involvement in 93% of patients with congenital hand anomalies. Twelve patients demonstrated congenital hand anomalies and 2 patients had been diagnosed with arthrogryposis. Among the 12 patients with congenital hand anomalies, 21 hands were classifiable as symbrachydactyly by the Oberg, Manske, and Tonkin classification and could be categorized by the Blauth and Gekeler classification. Short finger type was the most common subtype of symbrachydactyly, present in 13 hands. Eleven of these 13 patients (85%) were primarily affected on the radial side of the hand. Proximal arm involvement was identified in 2 patients with symbrachydactyly, both of whom had Poland syndrome and an absent pectoralis major. CONCLUSIONS: Symbrachydactyly in Möbius syndrome differs from the typical presentation of symbrachydactyly. Characteristically, there is a bilateral presentation with a strong predilection for radially based brachydactyly. These described characteristics may help the hand surgeon appropriately assess patients, especially those with radial-sided symbrachydactyly. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.