A framework for the evaluation of patients with congenital facial weakness.
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ABSTRACT:
SUBMITTER: Webb BD
PROVIDER: S-EPMC8028830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionCongenital 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.MethodsForty-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.ResultsMBS 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.DiscussionEDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.
| S-EPMC8353595 | biostudies-literature
Project description:Congenital facial weakness is present in a heterogeneous group of conditions. Among them is Moebius syndrome, which has been defined as a disorder with congenital, non-progressive facial weakness and limited abduction of one or both eyes. It is typically attributed to agenesis of the abducens and facial cranial nerves. This paper details ocular motor findings of 40 subjects (23 months to 64 years; 24 females, 16 males) with congenital facial weakness: 38 presented at a Moebius Syndrome Conference and two were clinic patients. A new classification scheme of patterns based on ocular motor phenotype is presented. Of 40 subjects, 37 had bilateral and three had unilateral facial weakness. The most common ocular motor pattern (Pattern 1, n=17, 43%) was bilateral horizontal gaze palsy with intact vertical range. Pattern 2 (n=10, 26%) was bilateral horizontal gaze palsy with variable vertical limitations. Pattern 3, which was rare, was isolated abduction deficits (n=2, 5%). Others had full motility range and did not meet minimal criteria for the diagnosis of Moebius syndrome (Pattern 4, n=10, 26%). One subject was too severely affected to characterize. Abnormal vertical smooth pursuit was present in 17 (57%) of 30 subjects: nine with Pattern 1, five with Pattern 2, and three with Pattern 4. Abnormal vertical saccades were present in 10 (34%) of 29 subjects. Vertical saccades appeared slow in nine: six with Pattern 1 and three with Pattern 2. Vertical saccades were absent in one subject with Pattern 2. Abnormal vertical optokinetic nystagmus was present in 19 (68%) of 28 subjects: 10 with Pattern 1, six with Pattern 2, one with Pattern 3, and two with Pattern 4. Reduced convergence was present in 19 (66%) of 29 subjects: nine with Pattern 1, six with Pattern 2, one with Pattern 3, and three with Pattern 4. The most common pattern of ocular motor deficit in Moebius syndrome is bilateral horizontal gaze palsy from pontine abducens nuclear defects, rather than abducens nerve involvement. Defects in the range or dynamic properties of vertical movements in subjects with congenital facial weakness may suggest involvement of ocular motor structures in the midbrain, including oculomotor nerves or nuclei, vertical supranuclear saccadic centres, and convergence neurons. Such deficits were found even in subjects with full vertical motility range. Classification of patterns of ocular motor deficits in congenital facial weakness may assist with further delineation of anatomic localization and identification of genetic deficits underlying these disorders.
| S-EPMC3959556 | biostudies-literature
Project description: Not available
| S-EPMC4316867 | biostudies-literature
Project description:In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome (n = 21), other congenital facial weakness disorders (n = 9) and healthy controls (n = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with high sensitivity (94%) and specificity (89%). Interestingly, this region was normal in congenital facial weakness subjects with oculomotor deficits of myopathic origin, who would have been classified as Moebius on the basis of purely clinical diagnostic criteria, indicating a potential role for diffusion MRI morphometry for differential diagnosis in this condition. When the entire Moebius syndrome cohort was compared to healthy controls, in addition to this 'landmark' region, other areas of significantly reduced volume in the brainstem emerged, including the location of the nuclei and fibres of cranial nerve VI (abducens nerve), and fibres of cranial nerve VII (facial nerve), and a more rostral portion of the medial longitudinal fasciculus. The high sensitivity and specificity of DTI-driven tensor-based morphometry in reliably detecting very small areas of volumetric abnormality found in this study suggest broader applications of this analysis in personalized medicine to detect hypoplasia or atrophy of small pathways and/or brainstem nuclei in other neurological disorders.
| S-EPMC7158234 | biostudies-literature
Project description:Congenital myopathies are an expanding spectrum of neuromuscular disorders with early infantile or childhood onset hypotonia and slowly or nonprogressive skeletal muscle weakness. RYR1 -related myopathies are the most common and frequently diagnosed class of congenital myopathies. Malignant hyperthermia susceptibility and central core disease are autosomal dominant or de novo RYR1 disorder, whereas multiminicore, congenital fiber type disproportion and centronuclear myopathy are autosomal recessive RYR1 disorders. The presence of ptosis, ophthalmoparesis, facial, and proximal muscles weakness, with the presence of dusty cores and multiple internal nuclei on muscle biopsy are clues to the diagnosis. We describe an 18-year-old male, who presented with early infantile onset ptosis, ophthalmoplegia, myopathic facies, hanging lower jaw, and proximal muscle weakness confirmed as an RYR1 -related congenital centronuclear myopathy on genetic analysis and muscle biopsy.
| S-EPMC10756716 | biostudies-literature
Project description:Central Core Disease (CCD) is a genetic neuromuscular disorder characterized by the presence of cores in muscle biopsy. The inheritance has been described as predominantly autosomal dominant (AD), and the disease may present as severe neonatal or mild adult forms. Here we report clinical and molecular data on a large cohort of Brazilian CCD patients, including a retrospective clinical analysis and molecular screening for RYR1 variants using Next-Generation Sequencing (NGS). We analyzed 27 patients from 19 unrelated families: four families (11 patients) with autosomal dominant inheritance (AD), two families (3 patients) with autosomal recessive (AR), and 13 sporadic cases. Biallelic RYR1 variants were found in six families (two AR and four sporadic cases) of the 14 molecularly analyzed families (~43%), suggesting a higher frequency of AR inheritance than expected. None of these cases presented a severe phenotype. Facial weakness was more common in biallelic than in monoallelic patients (p = 0.0043) and might be a marker for AR forms. NGS is highly effective for the identification of RYR1 variants in CCD patients, allowing the discovery of a higher proportion of AR cases with biallelic mutations. These data have important implications for the genetic counseling of the families.
| S-EPMC9141459 | biostudies-literature
Project description:ImportanceTotal ophthalmoplegia can result from ryanodine receptor 1 (RYR1) mutations without overt associated skeletal myopathy. Patients carrying RYR1 mutations are at high risk of developing malignant hyperthermia. Ophthalmologists should be familiar with these important clinical associations.ObjectiveTo determine the genetic cause of congenital ptosis, ophthalmoplegia, facial paralysis, and mild hypotonia segregating in 2 pedigrees diagnosed with atypical Moebius syndrome or congenital fibrosis of the extraocular muscles.Design, setting, and participantsClinical data including medical and family histories were collected at research laboratories at Boston Children's Hospital and Jules Stein Eye Institute (Engle and Demer labs) for affected and unaffected family members from 2 pedigrees in which patients presented with total ophthalmoplegia, facial weakness, and myopathy.InterventionHomozygosity mapping and whole-exome sequencing were conducted to identify causative mutations in affected family members. Histories, physical examinations, and clinical data were reviewed.Main outcome and measureMutations in RYR1.ResultsMissense mutations resulting in 2 homozygous RYR1 amino acid substitutions (E989G and R3772W) and 2 compound heterozygous RYR1 substitutions (H283R and R3772W) were identified in a consanguineous and a nonconsanguineous pedigree, respectively. Orbital magnetic resonance imaging revealed marked hypoplasia of extraocular muscles and intraorbital cranial nerves. Skeletal muscle biopsy specimens revealed nonspecific myopathic changes. Clinically, the patients' ophthalmoplegia and facial weakness were far more significant than their hypotonia and limb weakness and were accompanied by an unrecognized susceptibility to malignant hyperthermia.Conclusions and relevanceAffected children presenting with severe congenital ophthalmoplegia and facial weakness in the setting of only mild skeletal myopathy harbored recessive mutations in RYR1, encoding the ryanodine receptor 1, and were susceptible to malignant hyperthermia. While ophthalmoplegia occurs rarely in RYR1-related myopathies, these children were atypical because they lacked significant weakness, respiratory insufficiency, or scoliosis. RYR1-associated myopathies should be included in the differential diagnosis of congenital ophthalmoplegia and facial weakness, even without clinical skeletal myopathy. These patients should also be considered susceptible to malignant hyperthermia, a life-threatening anesthetic complication avoidable if anticipated presurgically.
| S-EPMC3865174 | biostudies-literature
Project description: Not available
| S-EPMC10467031 | biostudies-literature
Project description:Birth Defects: Moebius Syndrome and Related Facial Weakness Disorders
| PRJNA390828 | ENA
Project description:Classic infantile Pompe disease is an inherited generalized glycogen storage disorder caused by deficiency of lysosomal acid ?-glucosidase. If left untreated, patients die before one year of age. Although enzyme-replacement therapy (ERT) has significantly prolonged lifespan, it has also revealed new aspects of the disease. For up to 11 years, we investigated the frequency and consequences of facial-muscle weakness, speech disorders and dysphagia in long-term survivors. Sequential photographs were used to determine the timing and severity of facial-muscle weakness. Using standardized articulation tests and fibreoptic endoscopic evaluation of swallowing, we investigated speech and swallowing function in a subset of patients. This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months -12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease. To improve speech and reduce the risk for aspiration, early treatment by a speech therapist and regular swallowing assessments are recommended.
| S-EPMC3319904 | biostudies-literature