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The Jain COS Consortium., This study aims to determine clinically relevant phenotypic differences between the two most common phenotypic classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 and MMD1 are reported to involve different muscles, with LGMDR2 showing predominant limb girdle weakness and MMD1 showing predominant distal lower limb weakness. We used heatmaps, regression analysis and principle component analysis of functional and Magnetic Resonance Imaging data to perform a cross-sectional review of the pattern of muscle involvement in 168 patients from the Jain Foundation's international Clinical Outcomes Study for Dysferlinopathy. We demonstrated that there is no clinically relevant difference in proximal vs distal involvement between diagnosis. There is a continuum of distal involvement at any given degree of proximal involvement and patients do not fall into discrete distally or proximally affected groups. There appeared to be geographical preference for a particular diagnosis, with MMD1 being more common in Japan and LGMDR2 in Europe and the USA. We conclude that the dysferlinopathies do not form two distinct phenotypic groups and therefore should not be split into separate cohorts of LGMDR2 and MM for the purposes of clinical management, enrolment in clinical trials or access to subsequent treatments., The estimated $4 million USD needed to fund this study was provided by the Jain Foundation. Volker Straub was supported by an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1.

Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation., Congenital myasthenia syndrome; DOK7; limb-girdle weakness; sympathomimetics

X-linked spinal and bulbar muscular atrophy (SBMA, Kennedy disease) should be considered in the differential diagnosis of male patients with significant elevation of creatine kinase (CK), limb-girdle weakness, and hyporeflexia/areflexia.

Facioscapulohumeral dystrophy (FSHD), is a muscular dystrophy that classically affects the shoulder girdle and facial muscles. It should be considered in the differential diagnosis of patients presenting with limb girdle weakness. Progression is usually slow, and the condition is rarely fatal. Treatment is mostly supportive, although a number of patients can be helped with scapulo-thoracic fusion. This paper summarises the current understanding of this form of muscular dystrophy.

Item does not contain fulltext This first description of the oculopharyngeal muscular dystrophy (OPMD) phenotype in Dutch patients shows that limb girdle weakness can occur early in the course of disease and can give the first and major complaint in OPMD patients. The aim of this study was to examine clinically, histologically and genetically all Dutch OPMD patients known at the Neuromuscular Centre Nijmegen, to measure the limb girdle weakness (MRC scale) and to quantify the consequences of the limb girdle weakness on daily activities (Rankin scale). Remarkable in this population was the early onset and the severity of the limb girdle weakness. We found a higher percentage of patients with limb girdle weakness than reported before in non-Dutch OPMD populations. This limb girdle weakness caused limitations in daily activities more than the other symptoms of OPMD. It was difficult to compare the severity of the limb girdle weakness of Dutch patients with other patients because of the lack of data related to quantification of limb girdle weakness in non-Dutch OPMD patients. Because of the influence of the limb girdle weakness on the daily activities of the patients, we recommend that more attention is paid to the proximal limb muscles in OPMD patients early in the course of the disease.

Introduction Oculopharyngeal muscular dystrophy (OPMD) presents with progressive ptosis, dysphagia and limb girdle weakness, and is caused by expansion of a trinucleotide tandem repeat within the gene encoding poly-(A) binding protein 2. Aim To review the clinical manifestations of all genetically confirmed patients with OPMD in Scotland identified since 2002, and to estimate the delay between symptom onset and diagnosis. Method Retrospective case note review. Results The authors identified 17 patients. The commonest first symptom was ptosis at about the age of 60 years. Three to 20 years elapsed from the onset of ptosis to OPMD diagnosis. In 14 (82%) patients, dysphagia had developed by the time of diagnosis, and four (24%) out of these 14 patients with dysphagia had undergone a decade of investigation and treatment for pharyngeal problems. Thirteen patients (77%) also had symptoms of limb girdle muscle weakness. Every patient had a first-degree relative with ptosis. Conclusions OPMD could have been diagnosed earlier in every patient in this case series. Greater awareness of OPMD among ophthalmologists, gastroenterologists and otolaryngologists may lead to earlier diagnosis, improved management and avoidance of unnecessary investigations.

The clinical, histopathological, ultrastructural and geographical data on 29 cases of oculopharyngeal muscular dystrophy (OPMD) identified by the authors in France in briefly presented. The mean age of the patients was 53.8 ± 8.1 years. Onset symptoms were ptosis ( 14 29 ), dysphagia ( 12 29 ) and limb girdle weakness ( 3 29 ). The evolution of the disease was always progressive and followed different clinical patterns. The main histological changes in muscle biopsies were atrophic angulated fibers ( 29 29 ) and rimmed vacuoles ( 25 29 ); muscle fiber necrosis was very rare ( 1 29 ). The characteristic nuclear inclusions made of 8.5-nm filaments were observed in all cases, and found in 2–5% of the nuclei in a given ultrathin section. They are the morphological marker of the disease.

The phenotype is reported of 20 patients with autosomal recessive or sporadic, pelvifemoral limb girdle muscular dystrophy (LGMD). Selective wasting of muscles was observed at the moderately advanced stage of illness. The pattern of weakness was uniform. Attention to clinical detail allowed the identification of a phenotype different from a hypothetical scheme of LGMD based on previous literature, and other causes of limb girdle weakness. These patients may represent yet another nosologic entity within the autosomal recessive dystrophies; molecular genetic studies are awaited. A limited magnetic resonance imaging (MRI) study of muscle was of little consequence. Although additional detail was obtained, no pathognomonic distribution of the dystrophic process was observed; interindividual variation existed even among closely matched siblings. The severity of MRI signal change did not consistently correlate with the degree of weakness in an individual. When a diagnosis is uncertain, however, the added detail may be useful. © 1994 John Wiley & Sons, Inc.

The phenotype of Becker muscular dystrophy (BMD) is highly variable, and thus the disorder might be underdiagnosed. In this study we have reviewed the undiagnosed cases among patients referred for suspected BMD in the period 1985–1995. At that time DNA analysis of the DMD gene was the only routinely available diagnostic test for patients suspected of having muscular dystrophy. Over the last decade sequencing techniques have been developed for the detection of small mutations in the DMD gene. Our aim was to investigate whether BMD had been genetically underdiagnosed in the early decade of DNA analysis and, if so, whether we could improve the diagnostic yield by applying new techniques. Previously, in 79 of 185 referrals for BMD testing no deletions or duplications had been found. The original requisition forms for DNA analysis were re-evaluated; Forty-six cases were excluded because clinical data were lacking or not suggestive for BMD or the patients were known to be deceased. In 33 cases the clinical information was compatible with BMD and those were considered potentially relevant for re-analysis of the DMD gene. Sequencing could be performed on 31 stored DNA samples. Six different mutations, including four novel ones, were found. Long term clinical follow-up in these adult males revealed that one patient was asymptomatic, one had mild symptoms and four had lost ambulation due to progressive limb girdle weakness. Conclusion: We conclude that extending DNA analysis by sequencing the DMD gene can be helpful in identifying BMD in male patients in whom previously no deletions or duplications were found. A delayed diagnosis can still be valuable for the proband or the relatives of the BMD patients.

Objective: To evaluate the reliability and accuracy of skeletal muscle computed tomography to correctly identify different muscular dystrophies manifesting with limb girdle weakness. Four evaluators assessed scans from 118 patients with limb girdle muscular dystrophy caused by mutations in seven different genes and from 32 controls. The conditions studied were scans of genetically confirmed cases of Becker muscular dystrophy (BMD) [ n = 28], LGMD2C-F (Sarcoglycanopathies) [ n = 11], LGMD2I [ n = 4], LGMD1B [ n = 26], LGMD2A [ n = 24], Bethlem myopathy [ n = 14] and LGMD2L [ n = 11]. The control group [ n = 32] consisted of patients affected by muscular dystrophies manifesting with limb girdle weakness in which the aforementioned muscular dystrophies were excluded. The scans were compared with the characteristic patterns described in literature. The overall interobserver agreement was poor ( κ = 0,27), with markedly higher scores for Becker muscular dystrophy ( κ = 0,51) and Bethlem myopathy ( κ = 0,59). The sensitivity to detect selective patterns in relation to the genetic diagnosis was 40% if all limb girdle muscular dystrophies were taken together. The specificity was 58%, positive predictive value (PPV) 77% and 1-negative predictive value (1-NPV) 79%. Markedly better scores were observed for Becker muscular dystrophy (sensitivity 91%, PPV 66%, 1-NPV 3%) and Bethlem myopathy (sensitivity 90%, PPV 69%, 1-NPV 1%). Our findings suggest that muscle computed tomography might be an adjunct to the clinical diagnosis of Becker muscular dystrophy and Bethlem myopathy. However, pattern recognition was cumbersome in the other limb-girdle muscular dystrophies.

We present a case of adult Pompe disease (acid maltase deficiency) with an uncommon clinical presentation characterized by severe fatigue and myalgia prior to the onset of limb girdle weakness. Remarkably, the muscle biopsy demonstrated selective involvement of type 1 muscle fibers. The cause and clinical effects of fiber type specific involvement are currently unknown, but the phenomenon might contribute to the clinical heterogeneity in Pompe disease and the variable response to enzyme replacement therapy. 2010 Elsevier B.V. All rights reserved.

SIX patients with chronic renal disease treated by renal transplantation 26–50 months previously have been followed clinically and electro-diagnostically. Patients who had parathaesiae before the operation no longer complained of this symptom after transplantation, and one also became free of neurological signs. Various types of nervous system manifestations were present in combination in four patients: peripheral neuropathy in one patient, symptoms of restless legs in two, limb girdle weakness in three and two patients had evidence of cerebral vascular disease. Two patients developed impotence.