Features Of Facioscapulohumeral Muscular Dystrophy Research Articles

The other face of facioscapulohumeral muscular dystrophy: Exploring orofacial weakness using muscle ultrasound.

One of the most distinct clinical features of facioscapulohumeral muscular dystrophy (FSHD) is facial weakness. It leads to diminished facial expression and functional impairments. Despite its clinical relevance, little else is known about orofacial muscle involvement. We therefore evaluated orofacial muscle involvement in a sizeable cohort of FSHD participants with muscle ultrasound. Muscle ultrasound images of the following orofacial muscles were scored visually and quantitatively: depressor anguli oris (DAO), orbicularis oris (OO), buccinator, temporalis, masseter, digastric, zygomaticus major and minor bilaterally, and the geniohyoid. Reliability analyses of both visual and quantitative evaluations were performed. Ultrasound results were correlated with other measures: the FSHD clinical score, facial weakness score, and facial function scale. We included 107 FSHD participants (male 54%; age 52 ± 14 years), of whom 92% showed signs of facial weakness. The reliability of visual ultrasound analysis varied widely (κ 0.0-1.0). Quantitative ultrasound reliability was high (intraclass correlation analysis ≥ 0.96). The DAO, buccinator, OO, temporalis, and zygomaticus minor muscles were affected most often (15%-39%). The digastric, geniohyoid, zygomaticus major, and masseter muscles were least often affected (<5%). The ultrasound compound score correlated weakly to moderately with other outcome measures used (ρ = 0.3-0.7). This study adds to the understanding of orofacial weakness in FSHD, confirming the involvement of the muscles of facial expression in FSHD using ultrasound. We showed that orofacial muscle ultrasound is feasible and reliable when quantitatively assessed. Future studies should evaluate orofacial muscle ultrasound longitudinally, alongside clinical and patient-reported facial weakness outcome measures, to assess their potential as outcome measures.

Clinical features of facioscapulohumeral muscular dystrophy 1 in childhood.

To explore the clinical course of patients presenting with facioscapulohumeral dystrophy type 1 (FSHD1) in childhood, with a view to identifying areas where they differed from older patients and where extra support or monitoring might be required. A retrospective case-notes review of children with FSHD1 seen at a tertiary paediatric neuromuscular centre between 2002 and 2016 was performed. Data collected included age at and nature of presentation, path to diagnosis, genetic testing results, motor function, and occurrence of extramuscular features and complications. Eighteen children (11 females, seven males; mean [SD] age at latest review 13y 10mo [3y 9mo], range 8-19y) from 16 families were identified. Age at onset of FSHD1 correlated with the size of deletion (r=0.81) and most presentations were in children either younger than 5 years or older than 10 years. Children with onset before 5 years were more likely to present with non-muscular symptoms and to develop extramuscular pathology, including developmental and psychiatric issues, hearing or visual impairments, and problems involving respiratory function and nutrition. No cases of epilepsy or cardiac arrhythmia were identified but two children died. The complexity and severity of FSHD1 presenting in early childhood underlines the importance of a multidisciplinary approach to the disorder. Young children often present with non-muscular pathology in facioscapulohumeral dystrophy type 1 (FSHD1), especially hearing loss. Age at onset in paediatric FSHD1 appears bimodal: under 5 years or in adolescence. Prolonged delays to diagnosis are common. Children with very early-onset FSHD1 may require nutritional and/or respiratory support. Developmental and psychiatric comorbidities are common.

Features of facioscapulohumeral muscular dystrophy in oral and maxillofacial region and MRI analysis of facial muscles

Objective: To investigate the manifestation of facioscapulohumeral muscular dystrophy (FSHD) in oral and maxillofacial region. Methods: A total of 12 patients diagnosed as FSHD and 20 healthy volunteers were included in the study. Their medical history was collected from these patients. The decayed missing filled teeth (DMFT), calculus index-simplified (CI-S), occlusal relationship, maximal opening of mouth and maximum bite force were recorded. The impressions were taken to measure the maximal hight of palate and the width of palate. The lateral cephalometric radiographs were also taken to measure the mandibular plane-frankfurt horizontal plane angle (MP-FH). They finally received oral and maxillofacial region MRI examination to observe the masseter muscle, medial pterygoid muscle and lateral pterygoid muscle. The data were analyzed by t-test or Wilcoxon signed ranks test. Results: There was no significant gender difference in FSHD group. The average age of treatment was (27.5 ± 8.1) years and the average age of onset was (15.7±7.5) years. Nine patients liked to eat soft foods, 4 patients had difficulties of closing eyes, 8 patients had difficulties of cheek-bulging, 10 patients showed pouty lips and 9 patients had mesio-malocclusion. DMFT (4.0±2.3), CI-S (5.8±2.1), male maximal hight of palate (20.5±2.1) mm , female maximal hight of palate (17.9±1.6) mm, MP-FH (31.8°±2.2°) of FSHD group were greater than those of the control group. Male width of palate (34.8±1.4) mm, female width of palate (33.7±1.5) mm, male maximum bite force (451.7 ± 39.0) N, female maximum bite force (326.7 ± 21.6) N, maximal opening of mouth (3.5 ± 0.4) cm of FSHD group were less than those of the control group (P <0.05). Maxillofacial MRI showed muscle asymmetr in 11 cases of masseter and 6 cases of medial pterygoid muscle, 5 cases of lateral pterygoid, and these muscle showed mild fatty infiltration mainly concentrating in the grade 0, grade 1 and grade 2. Conclusions: The FSHD patients have poor oral hygiene, low masticatory function, limited mouth opening, high palate and narrow arch and different degree of malocclusion. The patients' masseter muscle, medial pterygoid muscles and lateral pterygoid muscles exhibit asymmetrical atrophy and fatty infiltration.

Dystrophie musculaire facio-scapulo-humérale de type 2

IntroductionIn recent years, the advances of knowledge in clinical, genetic and epigenetic features of facioscapulohumeral muscular dystrophy (FSHD) allowed the identification of two forms of FSHD, the classical autosomal dominant FSHD type 1, and FSHD type 2 characterized by an identical clinical phenotype but associated with a different (epi)genetic defect. State of the artIn the large majority of FSHD1 patients, the identification of D4Z4 pathogenic contraction on a permissive chromosome 4 is sufficient for diagnosis, while FSHD2 diagnosis is complicated by the fact that the genetic defect associated with this disease is not known yet and a complete D4Z4 genotype and a D4Z4 specific methylation test are required. Indeed, FSHD2 patients display a non-contracted D4Z4 allele on chromosomes 4, at least one permissive chromosome 4QA and a profound hypomethylation of both chromosomes 4 and 10. A common pathophysiological pathway has been hypothesized for FSHD1 and FSHD2 in order to explain the identical clinical phenotype and the highly similar epigenetic changes found in patients affected by these diseases. According to this hypothesis, chromatin relaxation – due to pathogenic D4Z4 contraction in FSHD1 patients, and to important hypomethylation of this locus in FSHD2 patients – would allow the last D4Z4 unit to encode for a toxic DUX4 transcript. This transcript would be stable only when encoded from a permissive chromosome 4 carrying a polyadenylation signal immediately distal to the last D4Z4 unit on chromosome 4. PerspectivesSince, to express clinical phenotype, FSHD2 patients have to carry both 4QA chromosome and hypomethylated D4Z4 on chromosomes 4 and 10, digenic transmission has been hypothesized for this disease. The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene. ConclusionsThe identification, among patients carrying a FSHD phenotype, of FSHD2, a new disease with distinct (epi)genetic features but having a common pathophysiological pathway with FSHD1, suggests the possibility of developping new therapeutic strategies suitable for both diseases.

Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

FSHD myoblasts fail to downregulate intermediate filament protein vimentin during myogenic differentiation

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular di- sorder. The clinical features of FSHD include weakness of the facial and shoulder girdle muscles followed by wasting of skeletal muscles of the pelvic girdle and lower extremities. Although FSHD myoblasts grown in vitro can be induced to differentiate into myotubes by serum starvation, the resulting FSHD myotubes have been sho- wn previously to be morphologically abnormal. Aim. In order to find the cause of morphological anomalies of FSHD myotubes we compared in vitro myogenic differentiation of normal and FSHD myoblasts at the protein level. Methods. We induced myogenic differentiation of normal and FSHD myoblasts by serum starvation. We then compared protein extracts from proliferating myoblasts and differentiated myotubes using SDS-PAGE followed by mass spectrometry identification of differentially expressed proteins. Results. We demonstrated that the expression of vimentin was elevated at the protein and mRNA levels in FSHD myotubes as compared to nor- mal myotubes. Conclusions. We demonstrate for the first time that in contrast to normal myoblasts, FSHD myo- blasts fail to downregulate vimentin after induction of in vitro myogenic differentiation. We suggest that vi- mentin could be an easily detectable marker of FSHD myotubes.

O.20 A mouse model that recapitulates features of facioscapulohumeral muscular dystrophy

O.20 A mouse model that recapitulates features of facioscapulohumeral muscular dystrophy

D.P.1.01 Clinical features of facioscapulohumeral muscular dystrophy in Czech population

Background and aims: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by a progressive and often asymmetrical weakness and wasting of the facial, shoulder, and upper-arm muscles. The clinical manifestation is a highly variable. Weakness is appearing from infancy to the late adulthood. FSHD is associated with contractions of D4Z4 repeat on 4q35. Authors report the population of 38 genetically proven patients suffering from FSHD in Czech Republic. Methods: Molecular-genetic analysis of FSHD was based on enzyme digestion, separation of DNA by pulsed field gel electrophoresis, Southern blot, and hybridisation.

Facioscapulohumeral muscular dystrophy (Landouzy-Dejerine type) in a Nigerian female: A case report

Muscular dystrophy is not an uncommon entity in Nigerian medical clinics. The facioscapulohumeral type represents a rare variety of the disorder with its own distinctive characteristics but is not expected to have significant cardiac manifestations. The case report of a 17-year-old Nigerian female with facioscapulohumeral muscular dystrophy and significant cardiac dysfunction is presented and the relevant literature is reviewed. A 17-year-old Nigerian female presented with 18 month history of shortness of breath on mild to moderate exertion, generalized weakness, weight loss and abnormal gait. Leg swelling developed a few weeks prior to presentation. Intrauterine life and early childhood were uneventful while her family history was unremarkable. She had typical features of facioscapulohumeral muscular dystrophy but in addition demonstrated evidence of significant cardiac impairment, which is uncommon and not typically expected in this disorder. It is important for clinicians to comprehensively evaluate every patient presenting with a hitherto "clear "diagnosis in order to unmask unexpected associated clinical details.

The Clinical Features of Facioscapulohumeral Muscular Dystrophy Associated With Borderline (≥35 kb) 4q35 EcoRI Fragments

: The objectives of this study were to characterize the clinical features of facioscapulohumeral muscular dystrophy (FSHD) in patients with borderline (>/=35 kb) EcoRI fragments and to compare patients with borderline EcoRI fragments with FSHD patients harboring fragments of <35 kb. : Most patients with FSHD harbor 4q35 EcoRI fragments of less than 35 kb. The clinical findings in patients with borderline fragments are not well known. : The authors conducted a retrospective review of patients with FSHD followed at a regional neuromuscular center over a 12-year period. : Eleven patients with DNA-positive FSHD, found to harbor borderline (>/=35 kb) EcoRI fragments (group 1), were compared with 30 patients with fragments of <35 kb (group 2). Group 1 patients were less likely (18%) to present with the classic FSHD phenotype as compared with group 2 patients (63%). Statistically significant differences in clinical disease severity and manual muscle testing scores were noted between the 2 groups, with group 1 patients showing less severe weakness and disability at presentation. : Patients with borderline fragments are more likely to have a partial or less severe form of FSHD, probably resulting from a less disruptive DNA alteration at the 4q35 locus.

Facioscapulohumeral muscular dystrophy: the choice of a biopsy site.

The utilization of so-called standard muscles for biopsy in patients with the clinical features of facioscapulohumeral muscular dystrophy (FSH) often results in nondiagnostic pathologic findings. Five patients are presented who had biopsies of the supraspinatus muscle in addition to one of the standard muscles. The supraspinatus muscle was diagnostic in all five cases. The findings suggest that the supraspinatus muscle should be considered as the biopsy site of first choice in those patients in whom the clinical picture suggests facioscapulohumeral-type muscular dystrophy.