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Clinical Imaging Mar 2021We aim to review the imaging features of congenital cranial dysinnervation disorders. Characteristic imaging findings can define subtypes of these disorders through... (Review)
Review
We aim to review the imaging features of congenital cranial dysinnervation disorders. Characteristic imaging findings can define subtypes of these disorders through assessment of cranial nerves, extraocular muscles, orbital, and brain abnormalities. Duane retraction syndrome shows absent or hypoplasic 6th cranial nerve and preserved extraocular muscles (EOM). Mobius syndrome shows absent 7th and 6th cranial nerves, absence of facial colliculus, flattening of the dorsal aspect of the pons, hypoplasia of the pons and medulla, and flattening of the 4th ventricular floor. Congenital fibrosis of the extraocular muscles reveals unilateral or bilateral hypoplasia or aplasia of the 3rd cranial nerve, atrophy of superior rectus and levator palpebrae superioris muscles, and atrophy of the brainstem and cerebellar hemispheres. Horizontal gaze palsy and progressive scoliosis show characteristic split pons sign, butterfly medulla, absent facial colliculi, and spinal scoliosis. HOXA1 Mutations show a bilateral absence of 6th cranial nerves with the underdeveloped inner ear. Pontine Cap Tegmental Dysplasia shows ventral pontine hypoplasia, dorsal tegmental projection into the 4th ventricle, and variable cranial nerve deficits.
Topics: Cranial Nerves; Duane Retraction Syndrome; Humans; Magnetic Resonance Imaging; Oculomotor Muscles; Radiologists
PubMed: 33189029
DOI: 10.1016/j.clinimag.2020.10.055 -
Psychiatria Danubina Sep 2019Mobius syndrome is characterized by a bilateral congenital paralysis of the facial and abducens nerves which leaves the subject with an expressionless "mask-like" face.
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.
Topics: Adult; Antipsychotic Agents; Diagnostic Errors; Facial Expression; Humans; Mobius Syndrome; Nonverbal Communication; Obsessive-Compulsive Disorder
PubMed: 31488755
DOI: No ID Found -
Orphanet Journal of Rare Diseases Dec 2022Congenital cranial dysinnervation disorders (CCDDs) are a group of diseases with high clinical and genetic heterogeneity. Clinical examinations combined with Magnetic...
BACKGROUND
Congenital cranial dysinnervation disorders (CCDDs) are a group of diseases with high clinical and genetic heterogeneity. Clinical examinations combined with Magnetic resonance imaging (MRI) and whole exome sequencing (WES) were performed to reveal the phenotypic and genotypic characteristics in a cohort of Chinese CCDDs patients.
RESULTS
A total of 122 CCDDs patients from 96 families were enrolled. All patients showed restrictive eye movements, and 46 patients from 46 families (47.9%, 46/96) were accompanied by multiple congenital malformations. Multi-positional high-resolution MRI was performed in 94 patients from 88 families, of which, all patients had hypoplasia of the cranial nerves except HGPPS patients and 15 patients from 15 families (17.0%,15/88) were accompanied by other craniocerebral malformations. WES was performed in 122 CCDDs patients. Ten pathogenic variants were detected in KIF21A, TUBB3, and CHN1 genes in 43 families. Three variants were unreported, including KIF21A (c.1064T > C, p.F355S), TUBB3 (c.232T > A, p.S78T) and CHN1 (c.650A > G, p.H217R). Of the 43 probands harboring pathogenic variants, 42 were diagnosed with Congenital Fibrosis of Extraocular Muscles (CFEOM) and one was Duane Retraction Syndrome (DRS). No definite pathogenic variants in known candidate genes of CCDDs were found in sporadic DRS, Möbius Syndrome (MBS) and Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) patients. The CFEOM patients harboring R380C, E410K and R262H variants in TUBB3 gene and F355S variant in KIF21A gene exhibited syndromic phenotypes.
CONCLUSIONS
This study broadened the phenotypic and genotypic spectrums of CCDDs, and it was the largest clinical and genetic investigation for CCDDs patients from China. KIF21A and TUBB3 were the common pathogenic genes in Chinese CFEOM. MRI coupled with WES can provide a supportive diagnosis in patients with clinically suspected CCDDs.
Topics: Humans; Congenital Cranial Dysinnervation Disorders; East Asian People; Duane Retraction Syndrome; Mobius Syndrome; Ophthalmoplegia; Fibrosis
PubMed: 36494820
DOI: 10.1186/s13023-022-02582-5 -
International Journal of Pediatric... Apr 2020Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current...
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.
Topics: 22q11 Deletion Syndrome; Adolescent; Arthritis; Arthrogryposis; Child; Child, Preschool; Chromosome Disorders; Cleft Palate; Clubfoot; Connective Tissue Diseases; De Lange Syndrome; Duane Retraction Syndrome; Female; Hand Deformities, Congenital; Hearing Loss, Sensorineural; Heart Defects, Congenital; Humans; Hypoventilation; Infant; Infant, Newborn; Intellectual Disability; Male; Mandibulofacial Dysostosis; Mobius Syndrome; Muscle Hypotonia; Pierre Robin Syndrome; Retinal Detachment; Retrospective Studies; Sleep Apnea, Central
PubMed: 31927149
DOI: 10.1016/j.ijporl.2019.109842 -
Orphanet Journal of Rare Diseases Apr 2021The epidemiology of Moebius syndrome (MBS) is difficult to assess. In the present study, we investigated the epidemiology of MBS in a well-defined population within a...
BACKGROUND
The epidemiology of Moebius syndrome (MBS) is difficult to assess. In the present study, we investigated the epidemiology of MBS in a well-defined population within a precise geographical area.
MATERIALS AND METHODS
Our university hospital is the only national referral center for the diagnosis and treatment of MBS. Participants in this cross-sectional study were patients affected by MBS who had been periodically followed by our medical staff since 1998. Most of the patients were referred to our hospital by the Italian Association of Moebius Syndrome (AISMO). Demographic data necessary for study purposes were made available in the AISMO database, updated to April 2018. Subjects were assigned to geographical macroareas that are conventionally used in surveys and epidemiological investigations by the Italian National Institute of Statistics. The rates and prevalence of MBS cases were calculated on the basis of the last available survey of the Italian population. Each study parameter was then calculated with reference to the whole country and macroarea partition. The sex rate and the corresponding prevalence were calculated with respect to the weighted whole population and to the respective sex population. Chi-square analysis was adopted to investigate possible differences among geographical regions and/or sexes. A p value < 0.05 was considered statistically significant.
RESULTS
One hundred and sixty-four out of 212 MBS patients fulfilled our inclusion criteria. All cases occurred in Caucasian patients and were sporadic. The median age at diagnosis was 3.6 years, ranging from 0 to 55 years; this range was significantly reduced to 0-5 years (median age at diagnosis: 2.2 years) in patients included after 2007. The calculated prevalence at birth was 0.06 cases per 10,000 live births, with an overall prevalence of 0.27/100,000, without any sex or geographical predominance.
CONCLUSIONS
The prevalence of MBS observed herein, rounded for possible underestimation, was 0.3/100,000 people, without any regional difference in the distribution of cases. Our data confirm the rarity of the disease on a national level.
Topics: Child, Preschool; Cross-Sectional Studies; Databases, Factual; Humans; Infant; Infant, Newborn; Italy; Mobius Syndrome; Prevalence
PubMed: 33827605
DOI: 10.1186/s13023-021-01808-2 -
Graefe's Archive For Clinical and... Jan 2021For some patients with complex ocular motility disorders, conventional strabismus surgery is insufficient. Surgery with tendon elongation allows correction of larger...
BACKGROUND
For some patients with complex ocular motility disorders, conventional strabismus surgery is insufficient. Surgery with tendon elongation allows correction of larger angles and maintains a sufficient arc of contact for rectus muscles. This study reports results for tendon elongation with bovine pericardium (Tutopatch®) in indications other than Graves' orbitopathy in which it is already widely used.
METHODS
We reviewed the records of all patients who underwent surgery with Tutopatch® in our institution. Angles of squint and head postures were analyzed preoperatively, on the first postoperative day, and in the long term (median 9 weeks after the operation). Patients with Graves' orbitopathy were excluded.
RESULTS
From 2011 to 2018, the procedures on 58 eyes of 54 patients (35 females, median age 35 years (3-75)) met the inclusion criteria. Horizontal rectus muscle surgery (53 eyes) was conducted on patients with residual strabismus (13), Duane's retraction syndrome with eso- (type I: 16)/exodeviation (type II: 2, type III: 1), 6th (7)/3rd nerve palsy (7), Möbius syndrome (2), congenital fibrosis of the extraocular muscles type 3A (CFEOM3A, TUBB3 mutation) (4), and orbital apex syndrome (1). Vertical rectus muscle surgery (5 eyes) was conducted on patients with myasthenia (1), vertical tropia after orbital floor fracture (1), CFEOM1 (2), and Parry-Romberg syndrome (1). 42 eyes had prior eye muscle surgery (1-5 procedures, median 1). Out of 45 patients with postoperative long-term data, 43 showed an angle reduction. Fifty-one percent had an angle of 10Δ (prism diopter) or less, one had a significant over-effect, and 10 had revision surgery. For the heterogeneous group of residual eso- and exotropias, the median absolute horizontal angle was reduced from 35Δ (16 to 45Δ) to 9Δ (0 to 40Δ), for Duane's retraction syndrome from 27.5Δ (9 to 40Δ) to 7Δ (0 to 40Δ), and for sixth and third nerve palsies from 43Δ (20 to 75Δ) to 18Δ (4 to 40Δ). For 3 patients with vertical rectus muscle surgery, the median absolute vertical angle was reduced from 30Δ (20 to 45Δ) to 4Δ (1 to 22Δ). The motility range was shifted in the direction contrary to the elongated muscle in all subgroups. A considerable reduction of the excursion into the field of action of the elongated muscle had to be registered.
CONCLUSIONS
Strabismus surgery with bovine pericardium introduces new surgical options for complicated revisions and for rare and complex oculomotor dysfunctions. Yet, it has to be recognized that this type of surgery aiming at maximum effects, despite preservation or restitution of the arc of contact, leads to reduction of the excursion into the field of action of the elongated muscle. Furthermore, dose finding can be difficult depending on the underlying pathology and more than one intervention might be necessary for optimal results.
Topics: Adult; Animals; Cattle; Female; Graves Ophthalmopathy; Humans; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Pericardium; Retrospective Studies; Strabismus; Tendons; Treatment Outcome
PubMed: 32949299
DOI: 10.1007/s00417-020-04939-7 -
[Zhonghua Yan Ke Za Zhi] Chinese... Jun 2022To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Cross-sectional study. The study enrolled 18...
To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Cross-sectional study. The study enrolled 18 sporadic MBS patients who visited the Eye Center of Beijing Tongren Hospital Affiliated to Capital Medical University from July 2018 to December 2021. All patients completed the general information questionnaire and underwent detailed ophthalmic examinations and general physical examinations. Seventeen patients received MRI examination of cranial nerves and the orbit. The peripheral venous blood of all patients and their nuclear family members was collected, the genomic DNA was extracted, and the pathogenic gene variations that may lead to MBS were identified by whole exome sequencing and bioinformatics analysis. Among the 18 patients, there were 8 males and 10 females, and the age was (4.5±4.0) years (range, 8 months to 17 years). All patients showed congenital, bilateral or unilateral abduction deficit and facial weakness, which met the minimum diagnostic criteria of MBS. Among them, bilateral abduction deficit (16/18) and bilateral facial weakness (15/18) were more common. Nine patients were orthotopic in primary position, eight presented with esotropia, and one showed hypotropia. All patients had ametropia, of which 4 patients were diagnosed as amblyopia. Fifteen patients were also accompanied by other multiple congenital malformations, mainly characterized by abnormal development of glossopharynx (14/18) and limbs (5/18), and 7 patients were also accompanied by motor retardation. In addition, 9 patients had intrauterine exposure to adverse factors. Among the 17 patients who underwent MRI, 15 patients had bilateral hypoplasia of the abducens nerve, two had unilateral hypoplasia of the abducens nerve, 14 showed bilateral hypoplasia of the facial nerve, and three showed hypoplasia of the left facial nerve. Besides, some patients were also accompanied by hypoplasia of other cranial nerves, mainly the glossopharyngeal nerve and the hypoglossal nerve. No definite pathogenic variations were found by whole exome sequencing and bioinformatics analysis. The main clinical features of MBS were congenital abduction deficit and facial weakness, with complicated manifestations and variable severity. MRI showed absence or thinning of the abducens nerve and the facial nerve. The results of MRI can be used as a supplement to the diagnostic criteria of MBS. The mutation detection rate of MBS was low, and half of patients had exposure to adverse factors during pregnancy, suggesting that there was a multifactorial pathogenic mechanism in MBS.
Topics: Cross-Sectional Studies; Facial Paralysis; Female; Humans; Infant; Male; Mobius Syndrome; Strabismus; Exome Sequencing
PubMed: 35692026
DOI: 10.3760/cma.j.cn112142-20220314-00108 -
The Journal of Hand Surgery Jul 2019To investigate the distinguishing morphological characteristics of the upper extremities in children 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.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Hand Deformities, Congenital; Humans; Male; Mobius Syndrome; Prevalence; Radiography; Retrospective Studies
PubMed: 31031024
DOI: 10.1016/j.jhsa.2019.02.020 -
Muscle & Nerve Apr 2021Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and...
INTRODUCTION
Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and myopathic disorders. Moebius syndrome is one type of CFW. In this study we explored the utility of electrodiagnostic studies (EDx) in the evaluation of individuals with CFW.
METHODS
Forty-three subjects enrolled prospectively into a dedicated clinical protocol and had EDx evaluations, including blink reflex and facial and peripheral nerve conduction studies, with optional needle electromyography.
RESULTS
MBS and hereditary congenital facial paresis (HCFP) subjects had low-amplitude cranial nerve 7 responses without other neuropathic or myopathic findings. Carriers of specific pathogenic variants in TUBB3 had, in addition, a generalized sensorimotor axonal polyneuropathy with demyelinating features. Myopathic findings were detected in individuals with Carey-Fineman-Ziter syndrome, myotonic dystrophy, other undefined myopathies, or CFW with arthrogryposis, ophthalmoplegia, and other system involvement.
DISCUSSION
EDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.
Topics: Adult; Diagnosis, Differential; Facial Paralysis; Female; Heterozygote; Humans; Male; Mobius Syndrome; Muscular Diseases; Mutation; Pierre Robin Syndrome
PubMed: 33389762
DOI: 10.1002/mus.27159 -
The Journal of Clinical Endocrinology... Jan 2022Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of...
CONTEXT
Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of NAFLD, but the mechanism of NAFLD is not completely understood. β-Tubulin is essential in mitoses, neuronal migration, and axon guidance during neuronal development. Pathogenic variants in the TUBB3 gene were shown to be associated with a wide spectrum of neurological abnormalities, but not accompanied by hepatic complications, such as NAFLD.
OBJECTIVE
This work aims to examine the association between TUBB3 mutation and nonalcoholic steatohepatitis (NASH).
METHODS
An 11-year-old girl has been followed up as having atypical Möbius syndrome since infancy, as she was born with bilateral ptosis, paralytic strabismus, and facial weakness. At age 7 years, she was diagnosed with TUBB3 E410K syndrome by whole-exome sequencing. At age 10 years, her blood examination revealed elevated liver transaminase levels, which persisted for almost 2 years. She underwent liver biopsy, the results of which were suggestive of NASH.
RESULTS
The expression of TUBB3 was absent, but that of tyrosine hydroxylase (TH) was present in the parenchymal nerve fibers of the liver. On the other hand, in comparison with an autopsy case of NASH and a normal control, these showed coexpression of TUBB3 and TH in the liver.
CONCLUSION
We report the first case of TUBB3 E410K syndrome accompanied by NASH. This case suggests that the TUBB3 mutation may be associated with the pathogenesis and progression of NASH in humans.
Topics: Age of Onset; Child; Female; Humans; Mutation; Non-alcoholic Fatty Liver Disease; Prognosis; Tubulin; Exome Sequencing
PubMed: 34435630
DOI: 10.1210/clinem/dgab628