Progressive Proximal Myopathy Research Articles

O08 Severely pruritic juvenile dermatomyositis

Abstract A 7-year-old female with type IV skin and autism spectrum disorder presented with a 4 month history of progressive proximal myopathy, weight loss and 20 month history of a worsening, intensely pruritic rash. Cutaneous examination showed a widespread eczematous eruption, post-inflammatory hypopigmentation, heliotrope rash and firm subcutaneous changes, in addition to palmar-plantar papules, pustules and burrows. Extra-cutaneous findings included multiple fixed flexion deformities and muscle wasting. Investigations revealed a normocytic anaemia, elevated muscle enzymes, strongly positive anti-nuclear antibodies and negative myositis-specific antibodies. Whole body MRI reported proximal muscle oedema. Skin biopsy demonstrated lichenoid and perifollicular inflammation, dermal mucin and subcutaneous calcification. Clinical findings were consistent with a diagnosis of juvenile dermatomyositis (JDM), complicated by concurrent scabies. Prednisolone in combination with methotrexate was commenced as first-line therapy in line with current consensus JDM treatment plans, in addition to topical steroids and sun protection. Muscle power started to improve after 5 months but ongoing cutaneous inflammation prompted second-line therapy with IV immunoglobulin. Oral ivermectin was required for the management of scabies due to topical permethrin failure. JDM is a rare autoimmune small-vessel vasculopathy with significant morbidity and limited evidence-based guidelines. Unlike adult-onset disease there is no racial predilection or association with malignancy. Calcinosis is more common in children but early treatment reduces disease complications. JDM has a variable disease course with a median time to remission of 4.67 years. Residual skin changes are increasingly recognised to be an early predictor of prolonged recovery time and these patients may benefit from biologic agents.

Dermatomyositis – A Rare Case with Excellent Outcome

Dermatomyositis and Polymyositis are autoimmune rheumatologic diseases with prominent feature of inflammatory myopathy. When the characteristic cutaneous manifestations coexist with myositis it is called dermatomyositis, otherwise it is polymyositis. There are also differences in histological findings. A 25-years-old lady presented with characteristic skin rash and progressive inflammatory proximal myopathy. The patient had difficulty in Activity of Daily Living (ADL) and ultimately she was unable to walk and became bed bound. Her muscle enzymes were very high, MRI and Electromyography (EMG) showed features of inflammatory myopathy (myositis). Muscle biopsy showed typical findings of dermatomyositis. She responded well with steroid and immunosuppressive drug along with exercise, physiotherapy and rehabilitation therapy. Now she is leading almost normal life with minimum maintenance dose of prednisolone and azathioprine. JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 91-94

The role of nephrologists in management of hypokalemic periodic paralysis: a case report

BackgroundHypokalemic periodic paralysis is a chronic condition characterized by sporadic attacks of weakness associated with acute hypokalemia. Attacks are typically associated with specific triggers, such as prolonged rest following exercise or consumption of a high-carbohydrate meal. Most commonly, this condition is caused by an autosomal dominant calcium channel mutation, and patients typically have an established family medical history of hypokalemic periodic paralysis. Long-term complications include the development of progressive proximal myopathy. Oral potassium chloride may be considered for the treatment of an acute attack, with administration of acetazolamide or dichlorphenamide as long-term prophylaxis. Nephrologists can play an important role in the recognition and treatment of previously undiagnosed hypokalemic periodic paralysis.Case presentationWe summarize the case of a 19-year-old white man who presented to the emergency department with undiagnosed attacks of hypokalemic periodic paralysis, and who reported, at follow-up, improvement in the severity and frequency of attacks with dichlorphenamide.ConclusionsThis case demonstrates the crucial role nephrologists can play, not only in the diagnosis of hypokalemic periodic paralysis, but also in the ongoing management of this condition. Patients should be advised to regularly follow up with their nephrology team for evaluation due to the risk of developing myopathy.

Respiratory failure and sleep-disordered breathing in late-onset Pompe disease: a narrative review.

Late-onset Pompe disease (LOPD) is a rare autosomal recessive glycogen storage disease that results in accumulation of glycogen in muscle cells causing muscular weakness. It causes a progressive proximal myopathy, accompanied by respiratory muscle weakness, which can lead to ventilatory failure. In untreated LOPD, the most common cause of death is respiratory failure. Patients suffering from respiratory compromise may present with symptoms of sleep-disordered breathing (SDB) before overt signs of respiratory failure. Diaphragm weakness leads to nocturnal hypoventilation, which can result in sleep disruption. Both subjective and objective sleep quality can be impaired with associated excessive daytime sleepiness (EDS). Health-related quality of life worsens as sleep disturbance increases. The mainstay of treatment for SDB and respiratory failure in LOPD is non-invasive ventilation (NIV), which aims to ensure adequate ventilation, particularly during sleep, and prevent acute hypercapnic failure. These patients are at risk of acute deterioration due to lower respiratory tract infections; effective secretion clearance and vaccination against common pathogens is an important facet of care. Whilst disease-modifying enzyme replacement therapy (ERT) delays progression of locomotor dysfunction and prolongs life, its effect on respiratory function and SDB remains unclear. There are no data demonstrating the impact of ERT on sleep quality or SDB.

LIMB GIRDLE MUSCULAR DYSTROPHIES: P.135 The 7-year progression of proximodistal dysferlinopathy in another Acadian patient from the Maritimes

Dysferlinopathies represent several pathologies caused by mutations in the DYSF gene. The two main phenotypes are Limb-girdle muscular dystrophy (LGMD) type 2B and distal Miyoshi's myopathy, but a proximodistal phenotype accounts for 6-35% of dysferlinopathies. The Acadians were French colonists who settled in the Canadian Maritimes and incurred the Great Deportation. Those who eluded capture remained mostly along the Maritime coastlines, preluding a higher regional prevalence of some recessive diseases. Dysferlinopathies are estimated to represent 35-45% of all LGMD's in the Acadian population. We report the case of a 19-year-old Acadian, who presented with substantially elevated serum creatine kinase levels at age 13, before the occurrence of rapidly declining distal posterior leg and limb-girdle myopathy during puberty. The patient has been followed for seven years providing clinical, imaging and laboratory documentation of disease progression. The absence of dysferlin, pathogenic homozygous DYSF mutations, and two homozygous TTN mutations were found. The parents were 3rd degree cousins and no extended family members were symptomatic. Finally, we compared the clinical phenotypes of nine unpublished cases of dysferlinopathy in Acadian patients from the Maritimes. Similar to previously reported cases of proximodistal dysferlinopathy, our patient showed macrophage infiltration on histology, and a fast disease progression supported by MRI series and clinical observations. The majority of Acadian cases, from three different DYSF mutations, also presented with a proximodistal phenotype. Modifier genes, environmental factors, or other unknown mutations have been proposed to explain phenotypic variability. Our patient had two homozygous mutations in A-band TTN, a gene region previously linked to distal myopathy. Proximodistal dysferlinopathy should be considered as a rare but plausible diagnosis in Acadian patients presenting with progressive distal and proximal myopathy.

Clinical Profile and Outcome of Pediatric Mitochondrial Myopathy in China.

Introduction: Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking.Patients and Methods: In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China.Results: Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified. Fourteen patients were found to harbor mitochondrial DNA point mutations (14/21, 66.7%), including m.3243A>G (9/15, 60%), m.3303C>T (2/15, 13.3%), m.3302A>G (1/15, 6.7%), m.3250T>C (1/15, 6.7%), m.3251A>G (1/15, 6.7%), of whom 12 patients presented with progressive proximal mitochondrial myopathy (12/14, 85.7%). Three patients revealed large-scale deletion in blood or muscle tissue (3/21, 14.3%), presenting with Kearns-Sayer syndrome (1/3, 33.3%) or chronic progressive external ophthalmoplegia (2/3, 66.7%). Four patients were found to harbor pathogenic nuclear gene variants (4/21, 19.0%), including five variants in TK2 gene and two variants in SURF1 gene. During the follow-ups up to 7 years, 10 patients developed cardiomyopathy (10/21, 47.6%), 13 patients occurred at least once hypercapnic respiratory failure (13/21, 61.9%), six experienced recurrent respiratory failure and intubation (6/21, 28.6%), eight patients failed to survive (8/21, 38.1%). With nocturnal non-invasive ventilation of BiPAP, three patients recovered from respiratory failure, and led a relative stable and functional life (3/21, 14.3%).Conclusion: Mitochondrial myopathy in children has great clinical, pathological, and genetical heterogeneity. Progressive proximal myopathy is most prevalent. Mitochondrial DNA point mutations are most common. And respiratory failure is a critical risk factor of poor prognosis.

Concurrent anti-PM-Scl antibody-associated systemic sclerosis and inclusion body myositis – report of two cases and review of the literature

ObjectivesTo describe two cases of anti-PM-Scl antibody-associated systemic sclerosis with evidence of inclusion body myositis on muscle biopsy. MethodsTwo female patients with anti-PM-Scl antibody-associated systemic sclerosis developed progressive proximal myopathy. Both patients had profound muscle weakness that was refractory to treatment with glucocorticoids with or without other oral immunosuppressive agents. Quadriceps muscle biopsy in both cases indicated inclusion body myositis (IBM). Monthly intravenous immunoglobulin (IVIG) infusions were added to the treatment regimen. ResultsOne patient's myopathy appears to have temporarily stabilized with IVIG infusions (2 g/Kg) every four weeks, though severe residual muscle weakness has persisted. The other patient's myopathy continues to progress slowly, despite being on 4-weekly IVIG infusions, along with weekly oral methotrexate and 6-monthly rituximab infusions. In this report, we compare these two patients with two similar cases that were previously reported and hypothesize a possible pathomechanism of this association. ConclusionThis extremely rare association of IBM and anti-PM-Scl antibody-associated scleromyositis sheds new light on the possible pathogenesis of IBM. It strengthens the hypothesis that autoimmune muscle disease can potentially trigger myodegeneration. Whether early intervention with aggressive immunosuppressive therapy can prevent progression to treatment-refractory IBM, should be a subject of future research.

MON-428 More Danger Than We Knew: Hypokalemic Periodic Paralysis Triggered by Alcohol Consumption

Introduction: Alcohol use disorder affects close to 20 million people in the United States. Alcohol causes long term damage in various organs including the muscles resulting in alcoholic myopathy. However, other less common etiologies for acute muscle weakness should be considered in these patients. Case presentation: Our patient is a 25 year-old Hispanic male, who presented with 2 hours of acute lower extremity weakness. He had difficulty walking, clothing, grasping and reported myalgia. He admitted to partying and binge drinking while consuming pizza and burgers the night before. He denied similar episodes in the past or any family history of weakness. His physical exam was remarkable for 2/5 strength in the hip flexors bilaterally, hip and knee extension was 4/5 bilaterally, knee flexion was 4/5 bilaterally. He had hyporeflexia, normal muscle bulk and tone and normal sensation. Diagnostic work up revealed a potassium of 1.9 mmol/L, phosphorus 1.9 mmol/L and CK of 176 IU/L (22-269 IU/L). Due to concern for thyrotoxic periodic paralysis, TSH was checked which was normal at 0.47 MCIU/ml (0.550-4.780 MCIU/ml). He was given 40meq IV potassium by slow infusion, followed by 40meq PO. His potassium improved to 2.4mmol/L after supplementation and there was a rapid recovery in his muscle weakness. Potassium levels were monitored for 24 hours. He had persistently normal potassium levels during his stay. His lower motor strength remained to be a 5/5 throughout the hospitalization. He was discharged with counseling and emphasis on alcohol cessation. Discussion: Beer contains 13 grams of CHO in 1 can. It’s high carbohydrate content can result in an insulin surge producing a rapid intracellular shift of potassium through N-K ATPase channels. This produces hypokalemic periodic paralysis (HPP) in predisposed patients. HPP is an uncommon neuromuscular disorder with 1 in 100,000 cases. It results from mutations in sodium, calcium and potassium channels in the skeletal muscles. It is an autosomal dominant disease and found predominantly in young Asian males. These patients are at risk for fatal cardiac arrhythmias due to their significantly low potassium levels on presentation. They carry the same risk for arrhythmias in the treatment period due to increased risk of over-correction resulting in hyperkalemia. Long term recurrent HPP can result in progressive proximal myopathy and reduced functional mobility that may affect quality of life. These short and long term complications in HPP can only be prevented by avoidance of triggers, in our case avoidance of alcohol consumption. Rapid recognition for close electrolyte monitoring and effective counseling by physicians to establish a clear understanding in patients is imperative for their long term health. (1)Vilarinho S, Siegel M D. Paralysis caused by a large carbohydrate meal. J Postgrad Med 2012;58:60-1

P.70 - Mitochondrial disorders in adults: clinical and genetic correlations in ten patients with nuclear DNA mutations

Mitochondrial diseases are multisystem heterogeneous disorders caused by dysfunction of the mitochondrial respiratory chain. They can be related to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). The diagnosis is essential for both genetic counseling as well as further treatment. Among 30 patients with multiple mtDNA deletions, nDNA mutations were confirmed in 8 patients. Additionally, 2 relatives of the already diagnosed patients were included in the study. Patients were assessed clinically, electrophysiologically and morphologically. The POLG and C10orf2 genes coding sequences analyses were performed. Different clinical syndromes were identified in examined patients: progressive external ophthalmoplegia (PEO) in 5, progressive external ophthalmoplegia plus proximal myopathy (PEO+) in 2, sensory ataxic neuropathy, dysarthria and ophthalmoparesis syndrome (SANDO) in 2 and myoclonic epilepsy in one. Electromyography studies presented myopathic pattern in 2 patients (with PEO and PEO+), in other it was normal. Ragged-red fibers were detected in 6 biopsies. Fibers devoid of cytochrome c oxidase activity were present in 3 of 6 investigated cases. Genetic analysis of POLG gene revealed following mutations in PEO: p.[Arg309Leu];[Gln968Glu], p.[Ala518Thr];[=] and p.[Trp748Ser];[Ser998Pro]. In PEO+ mutations: p.[Thr251Ile; Pro587Leu];[Thr251Ile;Pro587Leu] and p.[Thr251Ile;Pro587Leu];[Lys1191Asn] were present. In patients with SANDO syndrome the mutation p.[Arg290Cys];[Arg309Cys] was confirmed. And in patient with myoclonic epilepsy the mutation p.[Trp748Ser];[Trp748Ser] was detected. Additionally the analysis of the C10orf2 gene proved the mutation p.[Arg374Gln];[=] in two patients with PEO. Identification of nuclear genes mutations in adults is important for the evaluation of clinical spectrum and natural history of mitochondrial disorders.

A case report on an unusual case of gait abnormality

Vitamin D3 (cholecalciferol) is a fat-soluble vitamin that is essential for the skeletal health. Here, we discuss a case of a child from an upper middle-class family who presented with gradually progressive proximal myopathy and gait abnormality over 3 years. She was found to have severe vitamin D deficiency, resulting in proximal myopathy and pubic arch fractures with slipped capital femoral epiphysis, leading to the gait abnormality. In our country in spite of ample sunlight, vitamin D3 deficiency is rampant. The patient highlights the need of considering vitamin D deficiency as one of the differentials in myopathy and gait abnormalities in children.

Unmasking sarcoidosis following surgery for Cushing disease.

ABSTRACTWe present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.

Calf muscle hypertrophy in late onset pompe's disease

Pompe's disease (glycogen storage disease Type 2, acid maltase deficiency) is characterized by a progressive myopathy due to accumulation of glycogen in skeletal muscles in addition to various tissues. Late onset Pompe's disease is characterized by slowly progressive proximal myopathy with respiratory muscle involvement. We present the case of a 16-year-old female presenting with proximal muscle weakness with calf hypertrophy diagnosed to be late onset Pompe's disease. This case highlights the need to consider Pompe's disease in the differential diagnosis of calf muscle hypertrophy, in patients with proximal myopathy even without overt respiratory muscle involvement.

Prevalence of Asymptomatic Vertebral Fractures in Late-Onset Pompe Disease

Context: Bone fragility and low bone mass have been reported in small case series of patients with Pompe disease with severely reduced muscle strength or immobilization. Objective: Our objective was to determine the prevalence of morphometric vertebral fractures and to evaluate bone mass in adults with late-onset Pompe disease. Design: We conducted a multicenter cross-sectional observational study from August 2012 to December 2013. Study Setting: All subjects were outpatients referred to University Referral Centers. Patients: Patients included 22 late-onset Pompe disease patients with progressive proximal myopathy and minimal respiratory involvement without other diseases affecting bone mass. Main Outcome Measure: The prevalence of morphometric vertebral fractures was systematically assessed by semiquantitative analysis of lateral spine x-rays (T4–L5). Results: A high prevalence of morphometric vertebral fractures was found. At least 1 vertebral fracture was present in 17 of 22 patients (77%). All vertebr...

Prevalence of asymptomatic vertebral fractures in late-onset Pompe disease.

Bone fragility and low bone mass have been reported in small case series of patients with Pompe disease with severely reduced muscle strength or immobilization. Our objective was to determine the prevalence of morphometric vertebral fractures and to evaluate bone mass in adults with late-onset Pompe disease. We conducted a multicenter cross-sectional observational study from August 2012 to December 2013. All subjects were outpatients referred to University Referral Centers. PATIENTS included 22 late-onset Pompe disease patients with progressive proximal myopathy and minimal respiratory involvement without other diseases affecting bone mass. The prevalence of morphometric vertebral fractures was systematically assessed by semiquantitative analysis of lateral spine x-rays (T4-L5). A high prevalence of morphometric vertebral fractures was found. At least 1 vertebral fracture was present in 17 of 22 patients (77%). All vertebral fractures were asymptomatic. Bone mineral density was normal in 36.5% of the patients, whereas 36.5% were osteopenic and 27% were osteoporotic in at least 1 site. Fracture prevalence was independent of muscular and respiratory functional parameters and of genotype. Our data show for the first time that asymptomatic and atraumatic vertebral fractures occur frequently in late-onset Pompe disease patients without a significant impairment of bone mass. Screening for asymptomatic vertebral fractures should be routinely performed in Pompe disease irrespective of the disease severity. Fracture risk should be confirmed in longitudinal studies.

The clinical relevance of outcomes used in late-onset Pompe disease: can we do better?

Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. Clinical improvement was perceived by patients in 6 of the 10 studies. In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be evaluated specifically in late-onset Pompe disease and alternative outcome measures more specific to neuromuscular disease considered.

Gyrate atrophy of choroid and retina with myopia, cataract and systemic proximal myopathy: A rare case report from rural India

Gyrate atrophy is a rare metabolic disease with autosomal recessive inheritance pattern characterised by hyperornithinemia and typical ocular findings. This report presents a 17-year-old intellectually challenged girl consulting for a progressive fall of visual acuity with night blindness. Fundus examination showed patches of chorioretinal atrophy with typical scalloped borders and peri vascular pigmentation in the equatorial region. Fundus fluroscein angiography revealed characteristic staining pattern. Other ocular associations included myopia and posterior sub capsular cataract. Progressive systemic proximal myopathy was one of the associated features. Dietary supplementation of vitamin B6 was advised.

Variable Phenotypes of Knockin Mice Carrying the M712T Gne Mutation

GNE myopathy is a recessive adult onset, slowly progressive distal and proximal myopathy, caused by mutations in the GNE gene. The most frequent mutation in GNE myopathy patients is the Middle Eastern founder mutation M712T. We have generated Gne (M712T/M712T) knockin mice. A high mortality rate in the first generation due to renal failure was recorded (as previously described). However, the following Gne (M712T/M712T) offspring generations could be classified into 3 phenotypic categories: severe, mild and without apparent phenotype. By further crossing between mice with no apparent phenotype, we were able to establish a colony of Gne (M712T/M712T) knockin mice with a high- and long-term survival rate, lacking any renal phenotype. These mice did not present any muscle phenotype (clinical or pathological) for up to 18months. No correlation was found between the expression of any of the two mRNA Gne isoforms in muscle and the mouse genotype or phenotype. However, the expression of isoform 2 mRNA was significantly higher in the kidney of Gne (M712T/M712T) kidney affected mice compared with control. In contrast, the expression of UPR markers Bip, Chop and of the spliced form of XBP1, was upregulated in muscle of Gne (M712T/M712T) mice compared with controls, but was unchanged in the affected kidney. Thus, Gne defects can affect both muscle and kidney in mouse, but probably through different mechanisms.

Familial Clustering Strongly Suggests that the Phenotypic Variation of the 8344 A>G Lys Mitochondrial tRNA Mutation is Encoded in cis

The maternally inherited 8344 A>G mutation in the mitochondrial Lys tRNA is classically associated with the myoclonic epilepsy, ragged-red muscle fiber (MERRF) syndrome. Multiple lipomatosis (Madelung's disease) is occasionally described. Here we report a large kindred with a statistically significant clustering of very unusual clinical manifestations. We have studied a Greek family that includes seven symptomatic cases of 8344 A>G. Clinical features, glucose tolerance and heteroplasmy in fat, muscle and blood were analyzed. The patients, aged 34-76 at the time of assessment, all suffer from progressive proximal limb-girdle myopathy and extensive lipomatosis. Four of the seven have either impaired glucose tolerance or diabetes but none has had epilepsy, a cardinal feature of MERRF. Heteroplasmy was not higher in adipose tissue than that found in the literature. Compared to literature reports, the familial clustering of this unusual combination of manifestations (lipomatosis in all, epilepsy in none) is statistically significant. The clustering of unusual manifestations in this large kindred strongly suggests that much of the phenotypic variability of 8344 A>G is determined by mitochondrially encoded modifiers in cis.

BAG3 mutations: another cause of giant axonal neuropathy

Mutations in Bcl-2 associated athanogene-3 (BAG3) are a rare cause of myofibrillar myopathy, characterised by rapidly progressive proximal and axial myopathy, cardiomyopathy and respiratory compromise. Neuropathy has been documented neurophysiologically in previously reported cases of BAG3-associated myofibrillar myopathy and in some cases giant axons were observed on nerve biopsies; however, neuropathy was not thought to be a dominant feature of the disease. In the context of inherited neuropathy, giant axons are typically associated with autosomal recessive giant axonal neuropathy caused by gigaxonin mutations but have also been reported in association with NEFL- and SH3TC2-associated Charcot-Marie-Tooth disease. Here, we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy. Muscle magnetic resonance imaging (MRI) in one patient revealed mild to moderate atrophy without prominent selectivity. Examination of sural nerve biopsies in two patients demonstrated giant axons. This report confirms the association of giant axonal neuropathy with BAG3-associated myofibrillar myopathy, and highlights that neuropathy may be a significant feature.

Dermatomyositis

Dermatomyositis is an idiopathic acute inflammatory disorder, characterized by inflammation of skeletal muscle, progressive symmetrical proximal myopathy and classical cutaneous manifestations. It affects both children and adults, and women more frequently than men. Dermatomyositis is the commonest inflammatory myopathy in all age groups, with an estimated prevalence of 0.6-1.0 per 100 000 (Dalakas and Hohlfeld, 2003). Its association with malignancy mandates a thorough search for underlying neoplasia in all cases.