Prenatal diagnosis of Poland-Möbius syndrome by multimodality fetal imaging.

We describe prenatal diagnosis of Poland-Möbius syndrome using a combination of ultrasound and MRI. Poland syndrome was diagnosed based on absence of the pectoralis muscles associated with dextroposition of the fetal heart and elevation of the left diaphragm. Associated brain anomalies that led to the diagnosis of Poland-Möbius syndrome, included ventriculomegaly, hypoplastic cerebellum, tectal beaking, and a peculiar flattening of the posterior aspect of the pons and medulla oblongata, which has been reported by postnatal diffusion tensor imaging studies as a reliable neuroimaging marker for Möbius syndrome. Since abnormalities of cranial nerves VI and VII may be difficult to detect prenatally, careful attention to the appearance of the brain stem as illustrated in the current report may aid in the prenatal diagnosis of Möbius syndrome.

Echoencephalography of Möbius sequence: A congenital cranial dysinnervation disorder with brainstem calcifications.

BACKGROUND AND PURPOSE: Möbius sequence (MBS) previously known as Möbius syndrome is a rare nonprogressive developmental defect of the rhombencephalon leading to congenital abducens (VIth) and facial (VIIth) nerve palsy. Echoencephalography is the first, safe, noninvasive, and cost-effective imaging modality available at bedside. No study on the use of echoencephalography in neonates for the diagnosis of MBS has been previously reported. METHODS: In this single tertiary center study, more than 18,000 neonates underwent echoencephalographic imaging over the span of two decades. Imaging was performed through the anterior, posterior, and lambdoid fontanelles. All neonates found to have calcifications of brainstem tegmental nuclei underwent additional imaging studies. Each neonate with MBS was carefully examined by the same investigator. RESULTS: Five neonates were shown to have punctate, bilateral, symmetrical tegmental pontine calcifications through all three acoustic windows. These calcifications extended caudally in most patients, and rostrally in 2 patients. Brainstem hypoplasia was best seen through the posterior fontanelle. Three out of five infants were noted to have brainstem hypoplasia with straightening of the floor of the fourth ventricle. In two children, facial collicular bulges and hypoglossal eminences were present. All five infants fulfilled clinical diagnostic criteria of MBS. In addition, a wide array of cerebral defects is identified. Echoencephalographic findings were confirmed by other imaging modalities. CONCLUSION: Knowledge of echoencephalographic features of MBS should improve its early recognition. A detailed description of the various imaging phenotypes of MBS is necessary to characterize the etiology of this heterogeneous congenital cranial dysinnervation disorder.

Cephalometric Analysis of the Craniofacial Morphology in Patients With Moebius Syndrome.

BACKGROUND: Patients with Moebius syndrome may present a wide range of associated orofacial malformations, however, their craniofacial morphology has not been established via controlled cephalometric studies. OBJECTIVE: To present our institution's findings in the cephalometric evaluation in patients with Moebius syndrome. METHODS: Retrospective, cross-sectional study that included patients with Moebius syndrome over 9 years of age who had lateral cephalometric radiographs. Cephalometric analysis measurements of Ricketts, Steiner, and McNamara were performed. Quantitative data are expressed as mean and standard deviation, and qualitative data are expressed in totals and percentages. Comparative statistics between classic and incomplete Moebius and between patients older and younger than 16 years of age were performed. RESULTS: Twenty-four patients were included (54.2% females), mean age 17.46 ±â€Š8.85 years. Fifteen patients (62.5%) had classic Moebius syndrome, and nine (37.5%) had incomplete Moebius. Sixty-six percent of the patients presented either micrognathia or retrognathia, 95% showed mandibular hypoplasia, and 75% had a skeletal class II. Maxillary height was increased resulting in a vertical growth pattern. Upper and lower incisors tended towards proclination, and upper and lower lips protruded over cephalometric markings, and a long upper lip was evidenced in 41% of the patients. No significant differences were noted when comparing classic and incomplete Moebius syndrome. Patients younger than 16 years of age had significantly larger sella-nasion-A point and sella-nasion-B point angles, and a higher proportion of skeletal class II cases. CONCLUSIONS: Patients with Moebius syndrome have a vertical maxillary growth, micro or retrognathia, developing a skeletal class II and lip protrusion.

Neuroimaging Findings in Moebius Sequence.

BACKGROUND AND PURPOSE: Moebius sequence comprises a spectrum of brain congenital malformations predominantly affecting the function of multiple cranial nerves. Reported neuroimaging findings are heterogeneous and based on case reports or small case series. Our goal was to describe the neuroimaging findings of Moebius sequence in a large population of patients scanned with MR imaging. MATERIALS AND METHODS: An observational cross-sectional study was performed to assess brain MR imaging findings in 38 patients with Moebius syndrome studied between 2013 and 2016. RESULTS: Retrospective analysis of MR imaging studies showed flattening of the floor of the fourth ventricle floor secondary to a bilateral absent facial colliculus in 38 patients (100%) and unilateral absence in 1. A hypoplastic pons was found in 23 patients (60.5%). Mesencephalic malformations consisted of tectal beaking in 15 patients (39.5%) and increased anteroposterior midbrain diameter with a shallow interpeduncular cistern in 12 (31.6%). Infratentorial arachnoid cysts were found in 5 patients (13.2%), and cerebellar vermis hypoplasia, in 2 (5.3%). Supratentorial findings included the following: thalamic fusion (26.3%), periventricular nodular heterotopias (26.3%), ventriculomegaly (26.3%), callosal abnormalities (23.7%), and hippocampal malrotations (23.7%). CONCLUSIONS: Findings seen in this large patient cohort agreed with previously published reports. Flattening of the fourth ventricle floor secondary to a bilaterally absent facial colliculus was the most frequent MR imaging finding. The presence of other brain stem and cerebellar malformations as well as supratentorial abnormalities may help explain clinical symptoms and achieve a correct diagnosis.

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.

Möbius syndrome: clinico-radiologic correlation.

PURPOSE: Möbius syndrome is characterized by abducens and facial nerve palsy. However, the presence/absence of corresponding cranial nerves on MRI was not fully evaluated. The purpose of this study was to investigate the mechanism of Möbius syndrome by associating the presence of abducens and facial nerves on MR imagings with clinical features. METHODS: We retrospectively reviewed the medical records and MR imagings of nine patients with Möbius syndrome between January 2004 and October 2015. The presence/absence of abducens and facial nerves on MR imaging, as well as corresponding neuro-ophthalmologic clinical features, was investigated. RESULTS: Facial palsy was bilateral in six and unilateral in three patients. Abduction was limited bilaterally in five and unilaterally in four patients. The degrees of facial palsy and abduction limitation were variable, and asymmetric even in the bilateral cases. MR imaging documented bilateral absence of the abducens and facial nerves in six, absence of unilateral facial nerve and bilateral abducens nerves in one, and absence of facial and abducens nerves unilaterally on the same side in another. Both abducens and facial nerves were visualized bilaterally only in the one remaining patient. CONCLUSIONS: The absence of abducens and facial nerves on MR imaging was mostly correlated with the findings of facial palsy and abduction limitation in patients with Möbius syndrome. MR imaging aids in diagnosis of Möbius syndrome by documenting the absence or presence of abducens and facial nerves.

TUBB3 E410K syndrome with osteoporosis and cough syncope in a patient previously diagnosed with atypical Moebius syndrome.

BACKGROUND: A heterozygous c.1228G > A p.E410K mutation in TUBB3 encoding neuronal-specific ß-tubulin isotype 3 causes TUBB3 E410K syndrome, which exhibits a wide range of neurological and endocrinological abnormalities. CASE DESCRIPTION: The patient is a 31-year-old Japanese woman who was diagnosed with atypical Moebius syndrome because of congenital facial weakness and extraocular ophthalmoplegia sparing abduction. She suffered a femoral neck fracture at 23 years of age, and radiological and endocrinological studies revealed osteoporosis because of hypogonadotropic hypogonadism. She also had borderline intellectual disability, cyclic vomiting, syncope with cough, and decreased sense of smell since childhood. Brain magnetic resonance imaging revealed abnormal morphology of the corpus callosum and pontine. Hypoplastic bilateral oculomotor and facial nerves were evident. Based on these symptoms, we analyzed the TUBB3 gene and identified a heterozygous c.1228G > A (p.E410K) mutation that confirmed the diagnosis of TUBB3 E410K syndrome. CONCLUSION: TUBB3 E410K syndrome may be diagnosed as atypical Moebius syndrome because of overlapping clinical symptoms. Genetic analysis of c.1228G > A in TUBB3 is useful to differentiate TUBB3 E410K syndrome from other disorders presenting congenital external ophthalmoplegia and facial nerve palsy.

Estudio clínico, citogenético, molecular y de imagen de los pacientes con síndrome de Moebius del Hospital General 'Dr Manuel Gea González', Ciudad de México / Clinical, cytogenetic, molecular and image study of patients with Mobius syndrome at the General Hospital 'Dr Manuel Gea González', Mexico city

Introducción y Objetivo. El síndrome de Moebius es un trastorno congénito poco frecuente con prevalencia menor del 0.05%, caracterizado por parálisis facial congénita asociada a ausencia de abducción de los ojos por alteraciones del VI y VII nervios craneales, ya sea simétrica o asimétrica. La etiopatogenia cuenta con diferentes hipótesis: genética, vascular y teratógena. Existen pocos reportes en la literatura, y en especial en la latinoamericana, que describan las características clínicas y genéticas de estos pacientes. El presente estudio es el resultado del desarrollo de un equipo multidisciplinario en nuestro centro hospitalario para la descripción del espectro completo de la patología y así poder ofrecer los mejores tratamientos para cada uno de nuestros pacientes. Material y Método. Analizamos 115 pacientes con diagnóstico de síndrome de Moebius en sus 3 presentaciones: Moebius clásico, Moebius incompleto o Moebiuslike. Todos fueron sometidos a exploración física completa por un equipo multidisciplinario formado por ortopedistas, oftalmólogos, otorrinolaringólogos, ortodoncistas, neurólogos, pediatras, genetistas y cirujanos plásticos. Realizamos cariotipos a todos los pacientes para identificar anormalidades estructurales cromosómicas y enviamos muestras al Instituto Nacional de Medicina Genómica (INMeGen) para análisis molecular de cada paciente e identificación de posibles genes involucrados. Resultados. Un total de 52 pacientes (45%) fueron varones y 63 (55%) mujeres. Las manifestaciones clínicas fueron parálisis facial unilateral o bilateral con involucro de la abducción de los ojos en el 100%, asociada con estrabismo en el 62.6%, pie equino varo en el 46.1%, sindactilia simple 15.7%, paladar hendido 17.4%, micrognatia 17.4%, y síndrome de Poland 9.6%, entre otras manifestaciones. El análisis citogenético reportó 114 cariotipos de características estructurales normales y 1 solo caso de translocación recíproca balanceada entre el cromosoma 4 y 10. Dieciséis casos se asociaron a consumo materno de misoprostol en el primer trimestre del embarazo. El análisis molecular no se pudo concretar debido a falta de recursos materiales del INMeGen. Conclusiones. Hasta la fecha, y hasta donde hemos podido comprobar, esta es la cohorte de pacientes con síndrome de Moebius más grande reportada a nivel mundial en un solo centro hospitalario. La variabilidad de las presentaciones clínicas justifica el manejo por un equipo multidisciplinario tanto para el paciente como para los familiares. Este estudio abre las puertas para un campo de investigación mayor que nos pueda llevar a entender mejor la fisiopatología, intentar estableces causalidad y por lo tanto poder ofrecer mejores tratamientos, integrales y reproducibles (AU)

Background and Objective. Möbius syndrome is a rare congenital disease characterized by facial paralysis associated with an absence of abduction of the eyes for abnormalities in VI and VII cranial nerves. The pathogenesis has different hypothesis that include genetic, vascular and teratogenic causes. There are few reports in the literature and especially in Latin America to describe the clinical and genetic characteristics of these patients. The current study is the result of a multidisciplinary team developed in our center to describe the wide spectrum of the disease and offer the best treatment options to each of our patients. Methods. We analyzed 115 patients with the diagnosis of Möbius syndrome in its 3 presentations. All patients underwent a complete clinical examination by a multidisciplinary team formed by orthopedist, ophthalmologist, otolaryngologist, orthodontist, neurologist, plastic surgeon, pediatrician and geneticist. They underwent CTG banded karyotype to identify structural chromosome abnormalities. Results. Fifty two patients (45%) patients were male and 63 (55%) female. Clinical manifestations were found with unilateral or bilateral facial paralysis with VI nerve involvement in 100% of patients, associated with strabismus in 62.6%, 46.1% clubfoot, simple syndactyly 15.7%, 17.4% cleft palate, micrognathia 17.4%, Poland syndrome 9.6%, among others. Cytogenetic analysis showed normal karyotype in 114 patients and a reciprocal translocation between chromosome 4 and 10 in 1 patient. Sixteen cases of reported intake of misoprostol during the first trimester. Conclusions. As far as we know, this study is the largest global cohort reported in a single hospital of patients with Möbius syndrome. Variability of the clinical presentation justifies the management of these patients is a multidisciplinary team. This study opens the door for new studies that allow us to understand the pathophysiology of this disease and its response to different treatments (AU)

Brainstem calcification in Möbius syndrome.

Möbius syndrome is characterized by congenital facial diplegia, and may be associated with limb or orofacial malformations. A number of mechanisms have been proposed to explain the pathogenesis, including prenatal ischemia. We identified seven children with Möbius syndrome over the 10-year interval 1992-2001, all of whom manifested incomplete bilateral facial palsy. Associated limb and orofacial anomalies were observed in six cases. Computed tomographic scans were available in six children, and five of them manifested brainstem calcification which was most prominent in the floor of the fourth ventricle. The calcification was detected as early as 7 days of age and did not change with time, suggesting a static condition of prenatal onset. These observations support the hypothesis that the pathology in Möbius syndrome is secondary to prenatal brain ischemia.

Mobius syndrome: a case report.

Mobius Syndrome is characterized by showing unilateral facial nerve palsy of the sixth and seventh nerves, lack of facial expression, inability to smile and to tightly close the right eyelids. In this report, a 7-year-old-boy with Mobius syndrome is presented. He had asymmetry of facial expression, anomalies of fingers and severe tooth decay. After dental treatment, the periodic re-care visits should be done according to the eruption pattern.

Ectopic bone formation after temporal muscle transposition for facial paralysis.

This report describes the case of a patient with congenital bilateral facial paralysis in whom ectopic bone formation developed following temporal muscle transposition. Ectopic bone formation was first noticed 4 years after surgery. Whether the ossification is a result of the transfer of periosteum or the osteogenic capacity of muscular tissue is still unknown.